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Logo of actae2this articlesearchopen accesssubmitActa Crystallographica Section E: Crystallographic CommunicationsActa Crystallographica Section E: Crystallographic Communications
 
Acta Crystallogr E Crystallogr Commun. 2016 May 1; 72(Pt 5): 730–733.
Published online 2016 April 26. doi:  10.1107/S2056989016006563
PMCID: PMC4908523

Two ortho­rhom­bic polymorphs of hydro­morphone

Abstract

Conditions to obtain two polymorphic forms by crystallization from solution were determined for the analgesic drug hydro­morphone [C17H19NO3; systematic name: (4R,4aR,7aR,12bS)-9-hy­droxy-3-methyl-1,2,4,4a,5,6,7a,13-octa­hydro-4,12-methano­benzofuro[3,2-e]iso­quinolin-7-one]. These two crystalline forms, designated as I and II, belong to the P212121 ortho­rhom­bic space group. In both polymorphs, the hydro­morphone mol­ecules adopt very similar conformations with some small differences observed only in the N-methyl amine part of the mol­ecule. The crystal structures of both polymorphs feature chains of mol­ecules connected by hydrogen bonds; however, in form I this inter­action occurs between the hydroxyl group and the tertiary amine N atom whereas in form II the hydroxyl group acts as a donor of a hydrogen bond to the O atom from the cyclic ether part.

Keywords: crystal structure, polymorphism, hydro­morphone,hydrogen bonding

Chemical context  

Drug polymorphism has been the subject of hundreds of publications and numerous excellent reviews (Byrn et al., 1999  ; Grant, 1999  ; Singhal & Curatolo, 2004  ; Vippagunta et al., 2001  ). It is well established that polymorphs with different stability may have different solubility and dissolution rates, which can affect the bioavailability. The semi-synthetic opiate drug hydro­morphone is a potent derivative of morphine and despite poor bioavailability (Parab et al., 1988  ) is commonly used to treat moderate to severe pain in the treatment of cancer (Sarhill et al., 2001  ). To improve bioavailability of this compound a polymorph screen was performed that resulted in two solvent-free forms, designated as form I and form II.

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Object name is e-72-00730-scheme1.jpg

Structural commentary  

The mol­ecular structure of hydro­morphone in both polymorphs is nearly identical (Fig. 1  ) with some deviations found only for the N-methyl amine part of the piperidine fragment (Fig. 2  ). For example the C10—C11—N12—C13 torsion angle is 178.5 (2)° for form I and 169.5 (2)° for form II. The adopted conformation is similar to the conformation observed for morphine (Bye, 1976  ; Scheins et al., 2005  ).

Figure 1
Mol­ecular structure and atom-numbering scheme for hydro­morphone in the crystals of form I (left) and form II (right). Displacement ellipsoids are shown at the 50% probability level.
Figure 2
Superposition of the hydro­morphone mol­ecules from two polymorphic forms (red form I, blue form II) generated by fitting of the aromatic ring.

Supra­molecular features  

Although both polymorphs crystallize in the same space group P212121 with the same number of mol­ecules in the asymmetric unit, they differ significantly in the packing features (Figs. 3  and 4  ). In form I, the hydrogen-bonded mol­ecules are arranged into chains that run along the a axis with adjacent mol­ecules in the chain related by translation. The hydroxyl group donates a hydrogen atom which is accepted by the free electron pair of the N atom (Fig. 5  , Table 1  ). In the crystals of form II, inter­molecular hydrogen bonds also generate a chain of mol­ecules that propagates along the a axis; however, adjacent mol­ecules along this chain are related by a 21 symmetry axis. The mol­ecules are connected by O—H(...)O hydrogen bonds with the hydroxyl group as donor and the etheric O atom as acceptor (Table 2  ). These chains form a zigzag pattern, as illustrated in Fig. 6  . The packing arrangement of mol­ecules in form II is more dense than in polymorph I, as indicated by the Kitajgorodskij (1973  ) packing coefficients of 0.71 and 0.69, respectively.

Figure 3
Crystal packing diagram of form I, viewed along the a axis. Hydrogen bonds are shown as blue lines.
Figure 4
Crystal packing diagram of form II, viewed along the a axis. Hydrogen bonds are shown as blue lines.
Figure 5
The chain of mol­ecules running along the a axis formed by O—H(...)N hydrogen bonds in form I.
Figure 6
The zigzag chain of mol­ecules running along the a axis formed by O—H(...)O hydrogen bonds in form II.
Table 1
Hydrogen-bond geometry (Å, °) for (I)
Table 2
Hydrogen-bond geometry (Å, °) for (II)

Synthesis and crystallization  

10.8 mg of hydro­morphone was dissolved in 1.8 mL THF/acetone (1/1, v/v) and left to evaporate slowly under ambient conditions. After several days, colorless prism-like crystals of form I (m.p. 549.8 K) appeared that were used for diffraction studies. Crystals of form II were obtained in the following way: 19.7 mg of hydro­morphone was suspended in 0.3 mL of 50/50 mixture of ethanol and toluene. The suspension was heated to 333 K and stirred for about one h until it became clear. Subsequently, the vial was cooled rapidly to 278 K and colorless block-like crystals (m.p. 550.2 K) precipitated that were used for diffraction studies.

Refinement  

The H atoms from the methyl group in form II were included from geometry and their isotropic displacement parameters refined. The remaining H atoms were found in a Fourier difference map and freely refined. The absolute configuration of hydro­morphone was known from the synthetic route. In the absence of significant anomalous scattering effects, Friedel pairs were merged. Crystal data, data collection and structure refinement details are summarized in Table 3  .

Table 3
Experimental details

Supplementary Material

Crystal structure: contains datablock(s) I, II. DOI: 10.1107/S2056989016006563/gk2659sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016006563/gk2659Isup2.hkl

Structure factors: contains datablock(s) II. DOI: 10.1107/S2056989016006563/gk2659IIsup3.hkl

CCDC references: 1474753, 1474752

Additional supporting information: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Crystal data

C17H19NO3Dx = 1.339 Mg m3
Mr = 285.33Melting point < 549.8 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
a = 8.9497 (6) ÅCell parameters from 9169 reflections
b = 11.0906 (6) Åθ = 1.0–32.6°
c = 14.2608 (9) ŵ = 0.09 mm1
V = 1415.49 (15) Å3T = 296 K
Z = 4Prism, colorless
F(000) = 6080.35 × 0.35 × 0.30 mm

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Data collection

Bruker KappaCCD diffractometer3088 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.031
Horizonally mounted graphite crystal monochromatorθmax = 28.5°, θmin = 3.4°
CCD scansh = −11→11
7054 measured reflectionsk = −11→14
3427 independent reflectionsl = −17→19

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Refinement

Refinement on F2Primary atom site location: difference Fourier map
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042Hydrogen site location: difference Fourier map
wR(F2) = 0.096All H-atom parameters refined
S = 1.05w = 1/[σ2(Fo2) + (0.0361P)2 + 0.2726P] where P = (Fo2 + 2Fc2)/3
3427 reflections(Δ/σ)max = 0.005
266 parametersΔρmax = 0.19 e Å3
0 restraintsΔρmin = −0.17 e Å3

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.91711 (18)0.7664 (2)0.17051 (12)0.0513 (5)
H1A0.993 (4)0.774 (3)0.213 (2)0.069 (10)*
C20.7893 (2)0.7337 (2)0.21531 (15)0.0337 (4)
C30.6543 (2)0.73164 (19)0.16755 (13)0.0318 (4)
O40.63079 (17)0.74990 (16)0.07223 (10)0.0409 (4)
C50.4813 (3)0.7006 (2)0.05538 (15)0.0369 (5)
H5A0.439 (3)0.745 (2)0.0007 (18)0.034 (6)*
C60.4906 (3)0.5664 (3)0.03355 (16)0.0455 (6)
O70.6063 (3)0.5185 (2)0.00966 (16)0.0692 (6)
C80.3484 (4)0.4980 (3)0.0485 (2)0.0555 (7)
H8A0.362 (4)0.413 (3)0.031 (2)0.073 (10)*
H8B0.271 (4)0.541 (3)0.006 (2)0.063 (9)*
C90.3038 (3)0.5078 (2)0.1523 (2)0.0464 (6)
H9A0.387 (4)0.480 (3)0.193 (2)0.057 (8)*
H9B0.220 (3)0.455 (3)0.166 (2)0.055 (8)*
C100.2671 (2)0.6384 (2)0.17446 (16)0.0334 (4)
H10A0.175 (3)0.660 (2)0.1390 (16)0.034 (6)*
C110.2315 (2)0.6636 (2)0.27875 (16)0.0365 (5)
H11A0.147 (3)0.610 (2)0.2993 (18)0.043 (7)*
N120.1698 (2)0.78799 (19)0.28457 (13)0.0381 (4)
C130.1274 (3)0.8219 (3)0.3807 (2)0.0555 (7)
H13A0.072 (4)0.750 (3)0.410 (2)0.068 (9)*
H13B0.216 (4)0.844 (3)0.417 (2)0.054 (8)*
H13C0.060 (4)0.893 (3)0.373 (2)0.073 (10)*
C140.2738 (3)0.8808 (2)0.24843 (19)0.0426 (6)
H14A0.221 (3)0.956 (3)0.251 (2)0.051 (8)*
H14B0.359 (3)0.888 (2)0.291 (2)0.046 (7)*
C150.3324 (3)0.8528 (2)0.15154 (17)0.0377 (5)
H15A0.251 (3)0.862 (3)0.105 (2)0.048 (7)*
H15B0.414 (3)0.912 (2)0.1341 (18)0.043 (7)*
C160.3942 (2)0.72389 (19)0.14723 (13)0.0291 (4)
C170.5225 (2)0.70844 (19)0.21381 (14)0.0289 (4)
C180.5145 (2)0.6740 (2)0.30675 (14)0.0315 (4)
C190.3642 (2)0.6356 (3)0.34492 (17)0.0417 (5)
H19A0.364 (3)0.548 (3)0.356 (2)0.058 (9)*
H19B0.341 (3)0.672 (3)0.406 (2)0.058 (8)*
C200.6499 (2)0.6686 (2)0.35428 (14)0.0335 (4)
H20A0.655 (3)0.640 (2)0.4198 (18)0.039 (6)*
C210.7821 (2)0.6994 (2)0.30952 (15)0.0350 (5)
H21A0.871 (3)0.693 (2)0.3430 (17)0.038 (6)*

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0239 (8)0.0907 (15)0.0393 (9)−0.0080 (8)0.0014 (7)0.0059 (9)
C20.0235 (9)0.0427 (12)0.0349 (10)0.0002 (9)0.0009 (8)−0.0005 (9)
C30.0293 (10)0.0393 (11)0.0269 (9)−0.0021 (8)0.0004 (8)0.0035 (8)
O40.0315 (8)0.0656 (11)0.0256 (7)−0.0051 (7)0.0000 (6)0.0068 (7)
C50.0321 (10)0.0511 (13)0.0276 (9)−0.0006 (10)−0.0047 (9)0.0035 (9)
C60.0490 (14)0.0573 (15)0.0301 (10)0.0061 (12)−0.0004 (11)−0.0045 (10)
O70.0662 (14)0.0728 (14)0.0687 (14)0.0171 (11)0.0256 (11)−0.0007 (11)
C80.0547 (16)0.0505 (16)0.0615 (17)−0.0015 (14)−0.0071 (14)−0.0212 (14)
C90.0390 (13)0.0362 (12)0.0640 (16)−0.0067 (10)−0.0001 (12)−0.0024 (11)
C100.0262 (9)0.0360 (11)0.0380 (11)−0.0030 (8)−0.0044 (9)0.0015 (9)
C110.0257 (10)0.0438 (12)0.0398 (11)−0.0059 (9)0.0004 (9)0.0046 (10)
N120.0266 (8)0.0487 (11)0.0389 (9)−0.0015 (8)0.0005 (8)−0.0058 (8)
C130.0374 (13)0.084 (2)0.0448 (14)−0.0071 (15)0.0034 (12)−0.0195 (14)
C140.0357 (12)0.0383 (13)0.0536 (14)0.0002 (10)0.0000 (11)−0.0055 (10)
C150.0339 (11)0.0353 (11)0.0438 (12)0.0003 (9)−0.0037 (10)0.0064 (9)
C160.0257 (9)0.0340 (10)0.0275 (9)−0.0015 (8)−0.0034 (8)0.0024 (8)
C170.0247 (9)0.0340 (10)0.0281 (9)−0.0015 (8)−0.0033 (8)0.0024 (8)
C180.0281 (9)0.0391 (11)0.0274 (9)−0.0019 (8)0.0000 (8)0.0040 (8)
C190.0291 (11)0.0599 (15)0.0363 (12)−0.0029 (10)0.0027 (10)0.0144 (11)
C200.0335 (11)0.0414 (11)0.0256 (9)−0.0002 (9)−0.0037 (8)0.0035 (8)
C210.0260 (9)0.0441 (12)0.0350 (10)−0.0003 (9)−0.0074 (9)−0.0006 (9)

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Geometric parameters (Å, º)

O1—C21.360 (3)C11—C191.548 (3)
O1—H1A0.91 (4)C11—H11A1.01 (3)
C2—C31.387 (3)N12—C131.472 (3)
C2—C211.398 (3)N12—C141.480 (3)
C3—C171.376 (3)C13—H13A1.03 (4)
C3—O41.390 (2)C13—H13B0.98 (3)
O4—C51.465 (3)C13—H13C1.00 (4)
C5—C61.523 (4)C14—C151.510 (3)
C5—C161.546 (3)C14—H14A0.96 (3)
C5—H5A1.00 (3)C14—H14B0.98 (3)
C6—O71.212 (3)C15—C161.534 (3)
C6—C81.498 (4)C15—H15A0.99 (3)
C8—C91.537 (4)C15—H15B1.01 (3)
C8—H8A0.99 (3)C16—C171.500 (3)
C8—H8B1.03 (3)C17—C181.381 (3)
C9—C101.519 (3)C18—C201.390 (3)
C9—H9A1.00 (3)C18—C191.512 (3)
C9—H9B0.97 (3)C19—H19A0.99 (3)
C10—C161.531 (3)C19—H19B0.98 (3)
C10—C111.546 (3)C20—C211.387 (3)
C10—H10A1.00 (2)C20—H20A0.99 (3)
C11—N121.488 (3)C21—H21A0.93 (3)
C2—O1—H1A110 (2)C14—N12—C11113.08 (18)
O1—C2—C3120.43 (18)N12—C13—H13A108.1 (19)
O1—C2—C21124.26 (19)N12—C13—H13B110.6 (17)
C3—C2—C21115.31 (18)H13A—C13—H13B111 (3)
C17—C3—C2120.96 (17)N12—C13—H13C105 (2)
C17—C3—O4111.48 (17)H13A—C13—H13C111 (3)
C2—C3—O4127.56 (18)H13B—C13—H13C110 (3)
C3—O4—C5104.13 (15)N12—C14—C15113.2 (2)
O4—C5—C6110.4 (2)N12—C14—H14A106.6 (17)
O4—C5—C16105.03 (16)C15—C14—H14A112.8 (17)
C6—C5—C16111.35 (19)N12—C14—H14B109.2 (16)
O4—C5—H5A106.7 (14)C15—C14—H14B108.4 (16)
C6—C5—H5A110.2 (14)H14A—C14—H14B106 (2)
C16—C5—H5A113.0 (14)C14—C15—C16110.72 (18)
O7—C6—C8122.9 (3)C14—C15—H15A109.5 (16)
O7—C6—C5122.2 (3)C16—C15—H15A109.6 (17)
C8—C6—C5114.8 (2)C14—C15—H15B110.0 (15)
C6—C8—C9108.8 (2)C16—C15—H15B109.6 (15)
C6—C8—H8A110 (2)H15A—C15—H15B107 (2)
C9—C8—H8A110 (2)C17—C16—C10109.73 (16)
C6—C8—H8B104.6 (18)C17—C16—C15110.92 (17)
C9—C8—H8B110.7 (18)C10—C16—C15107.40 (17)
H8A—C8—H8B112 (3)C17—C16—C597.53 (16)
C10—C9—C8108.9 (2)C10—C16—C5119.10 (18)
C10—C9—H9A109.6 (18)C15—C16—C5111.80 (17)
C8—C9—H9A110.5 (18)C3—C17—C18123.80 (18)
C10—C9—H9B111.4 (18)C3—C17—C16109.37 (17)
C8—C9—H9B110.3 (18)C18—C17—C16126.82 (18)
H9A—C9—H9B106 (2)C17—C18—C20115.76 (18)
C9—C10—C16112.16 (19)C17—C18—C19118.01 (18)
C9—C10—C11114.6 (2)C20—C18—C19125.99 (18)
C16—C10—C11106.56 (17)C18—C19—C11113.97 (18)
C9—C10—H10A107.5 (14)C18—C19—H19A109.8 (18)
C16—C10—H10A109.8 (14)C11—C19—H19A107.0 (18)
C11—C10—H10A106.0 (14)C18—C19—H19B113.1 (19)
N12—C11—C10107.31 (18)C11—C19—H19B107.2 (18)
N12—C11—C19115.9 (2)H19A—C19—H19B105 (2)
C10—C11—C19113.08 (19)C21—C20—C18120.57 (18)
N12—C11—H11A104.9 (15)C21—C20—H20A118.2 (16)
C10—C11—H11A109.1 (15)C18—C20—H20A121.2 (16)
C19—C11—H11A106.1 (15)C20—C21—C2123.27 (19)
C13—N12—C14108.0 (2)C20—C21—H21A118.1 (15)
C13—N12—C11112.6 (2)C2—C21—H21A118.5 (15)
C10—C11—N12—C13178.5 (2)

(I) (4R,4aR,7aR,12bS)-9-Hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]   Hydrogen-bond geometry (Å, º)

D—H···AD—HH···AD···AD—H···A
O1—H1A···N12i0.91 (4)1.89 (4)2.796 (3)171 (3)

Symmetry code: (i) x+1, y, z.

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Crystal data

C17H19NO3Dx = 1.388 Mg m3
Mr = 285.33Melting point < 550.2 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
a = 8.8802 (6) ÅCell parameters from 7368 reflections
b = 10.6208 (8) Åθ = 0.4–32.6°
c = 14.4733 (9) ŵ = 0.10 mm1
V = 1365.05 (16) Å3T = 296 K
Z = 4Block, colorless
F(000) = 6080.40 × 0.32 × 0.22 mm

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Data collection

Bruker KappaCCD diffractometer4693 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.022
Horizonally mounted graphite crystal monochromatorθmax = 32.6°, θmin = 3.8°
CCD scansh = −13→13
15227 measured reflectionsk = −16→16
4920 independent reflectionsl = −21→16

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Refinement

Refinement on F2Primary atom site location: difference Fourier map
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.033Hydrogen site location: mixed
wR(F2) = 0.095H atoms treated by a mixture of independent and constrained refinement
S = 1.07w = 1/[σ2(Fo2) + (0.0623P)2 + 0.0509P] where P = (Fo2 + 2Fc2)/3
4920 reflections(Δ/σ)max = 0.011
257 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = −0.12 e Å3

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.93240 (13)0.77706 (10)0.49050 (9)0.0470 (3)
H11.015 (3)0.792 (2)0.517 (2)0.069 (8)*
C20.94522 (14)0.66225 (11)0.44868 (8)0.0314 (2)
C30.82077 (12)0.60798 (11)0.40680 (7)0.02819 (19)
O40.67658 (10)0.65856 (9)0.39772 (7)0.03425 (18)
C50.60923 (12)0.58599 (11)0.32226 (8)0.0299 (2)
H50.500 (2)0.586 (2)0.3283 (14)0.039 (4)*
C60.64963 (14)0.64991 (13)0.23020 (10)0.0362 (2)
O70.68419 (15)0.76008 (11)0.22794 (10)0.0516 (3)
C80.6488 (2)0.56607 (16)0.14696 (10)0.0455 (3)
H8A0.549 (3)0.528 (2)0.1420 (15)0.048 (5)*
H8B0.681 (3)0.615 (2)0.0937 (18)0.058 (6)*
C90.75507 (16)0.45421 (14)0.16230 (8)0.0366 (3)
H9A0.856 (2)0.486 (2)0.1784 (15)0.048 (5)*
H9B0.759 (3)0.396 (3)0.1098 (19)0.065 (7)*
C100.69690 (13)0.37489 (11)0.24255 (7)0.0289 (2)
H100.601 (2)0.3431 (18)0.2251 (13)0.035 (4)*
C110.79909 (14)0.26306 (11)0.26841 (8)0.0322 (2)
H110.810 (2)0.2131 (17)0.2157 (12)0.033 (4)*
N120.71416 (14)0.18458 (10)0.33458 (8)0.0359 (2)
C130.7868 (2)0.06280 (15)0.35203 (14)0.0513 (4)
H13A0.80720.02170.29430.075 (8)*
H13B0.87960.07600.38470.090 (9)*
H13C0.72120.01100.38850.081 (8)*
C140.68139 (17)0.24994 (12)0.42125 (9)0.0367 (2)
H14A0.617 (3)0.1946 (18)0.4586 (14)0.044 (5)*
H14B0.769 (3)0.2710 (19)0.4580 (15)0.046 (5)*
C150.59734 (14)0.37270 (12)0.40416 (8)0.0323 (2)
H15A0.496 (2)0.3593 (17)0.3840 (13)0.034 (4)*
H15B0.592 (2)0.4201 (18)0.4616 (15)0.044 (5)*
C160.67804 (11)0.45335 (10)0.33092 (7)0.02580 (18)
C170.83077 (12)0.49110 (10)0.36541 (7)0.02626 (19)
C180.96269 (12)0.42399 (11)0.35670 (8)0.02859 (19)
C190.95925 (15)0.30434 (12)0.30011 (10)0.0356 (2)
H19A1.020 (3)0.318 (2)0.2452 (17)0.055 (6)*
H19B1.006 (3)0.233 (3)0.3363 (19)0.071 (7)*
C201.09004 (13)0.47869 (12)0.39737 (8)0.0325 (2)
H201.191 (2)0.4392 (19)0.3896 (13)0.039 (4)*
C211.07953 (14)0.59403 (12)0.44358 (8)0.0334 (2)
H211.170 (2)0.6333 (17)0.4688 (15)0.043 (5)*

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0399 (5)0.0442 (5)0.0569 (6)−0.0038 (4)−0.0079 (5)−0.0219 (5)
C20.0304 (5)0.0351 (5)0.0289 (5)−0.0049 (4)−0.0020 (4)−0.0040 (4)
C30.0249 (4)0.0316 (5)0.0281 (4)−0.0005 (4)0.0002 (4)−0.0050 (4)
O40.0277 (4)0.0350 (4)0.0400 (4)0.0037 (3)−0.0007 (3)−0.0119 (3)
C50.0232 (4)0.0327 (5)0.0337 (5)0.0021 (3)−0.0005 (4)−0.0050 (4)
C60.0263 (5)0.0402 (6)0.0421 (6)0.0046 (4)−0.0030 (4)0.0064 (5)
O70.0452 (6)0.0432 (6)0.0663 (7)−0.0039 (5)−0.0079 (5)0.0138 (5)
C80.0511 (8)0.0538 (8)0.0316 (5)0.0087 (7)−0.0034 (5)0.0080 (5)
C90.0400 (6)0.0445 (6)0.0254 (4)0.0030 (5)0.0035 (4)−0.0002 (4)
C100.0285 (5)0.0334 (5)0.0248 (4)−0.0008 (4)0.0007 (3)−0.0048 (3)
C110.0352 (5)0.0305 (5)0.0310 (5)0.0001 (4)0.0044 (4)−0.0064 (4)
N120.0415 (6)0.0285 (4)0.0378 (5)−0.0021 (4)0.0036 (4)−0.0025 (4)
C130.0601 (10)0.0338 (6)0.0602 (9)0.0061 (6)0.0052 (7)0.0034 (6)
C140.0438 (6)0.0357 (6)0.0306 (5)−0.0041 (5)0.0038 (5)0.0024 (4)
C150.0314 (5)0.0369 (5)0.0285 (4)−0.0044 (4)0.0065 (4)−0.0038 (4)
C160.0228 (4)0.0295 (4)0.0251 (4)−0.0013 (3)0.0012 (3)−0.0042 (3)
C170.0237 (4)0.0291 (4)0.0260 (4)−0.0012 (3)−0.0001 (3)−0.0029 (3)
C180.0248 (4)0.0308 (5)0.0301 (4)0.0018 (4)0.0008 (3)0.0003 (4)
C190.0296 (5)0.0331 (5)0.0441 (6)0.0039 (4)0.0046 (5)−0.0060 (4)
C200.0240 (4)0.0387 (5)0.0350 (5)0.0014 (4)−0.0020 (4)0.0045 (4)
C210.0272 (5)0.0412 (6)0.0320 (5)−0.0054 (4)−0.0056 (4)0.0014 (4)

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Geometric parameters (Å, º)

O1—C21.3660 (15)C11—C191.5574 (18)
O1—H10.84 (3)C11—H110.934 (17)
C2—C31.3860 (15)N12—C141.4629 (17)
C2—C211.3975 (18)N12—C131.467 (2)
C3—C171.3813 (14)C13—H13A0.9600
C3—O41.3948 (14)C13—H13B0.9600
O4—C51.4643 (14)C13—H13C0.9600
C5—C61.5379 (18)C14—C151.5225 (19)
C5—C161.5407 (16)C14—H14A0.98 (2)
C5—H50.98 (2)C14—H14B0.97 (2)
C6—O71.2101 (18)C15—C161.5398 (15)
C6—C81.498 (2)C15—H15A0.958 (19)
C8—C91.533 (2)C15—H15B0.97 (2)
C8—H8A0.97 (2)C16—C171.4998 (14)
C8—H8B0.97 (2)C17—C181.3770 (15)
C9—C101.5249 (17)C18—C201.4010 (16)
C9—H9A0.98 (2)C18—C191.5122 (16)
C9—H9B0.98 (3)C19—H19A0.97 (2)
C10—C161.5356 (14)C19—H19B1.01 (3)
C10—C111.5409 (17)C20—C211.3988 (18)
C10—H100.954 (19)C20—H201.00 (2)
C11—N121.4767 (16)C21—H210.98 (2)
C2—O1—H1107.5 (18)C13—N12—C11112.62 (12)
O1—C2—C3119.90 (11)N12—C13—H13A109.5
O1—C2—C21123.87 (11)N12—C13—H13B109.5
C3—C2—C21116.22 (10)H13A—C13—H13B109.5
C17—C3—C2120.81 (11)N12—C13—H13C109.5
C17—C3—O4111.37 (9)H13A—C13—H13C109.5
C2—C3—O4127.81 (10)H13B—C13—H13C109.5
C3—O4—C5104.03 (8)N12—C14—C15111.38 (10)
O4—C5—C6108.58 (10)N12—C14—H14A107.6 (12)
O4—C5—C16104.99 (9)C15—C14—H14A108.4 (12)
C6—C5—C16112.43 (9)N12—C14—H14B114.9 (13)
O4—C5—H5109.9 (12)C15—C14—H14B106.6 (12)
C6—C5—H5108.1 (12)H14A—C14—H14B107.7 (17)
C16—C5—H5112.8 (13)C14—C15—C16111.10 (10)
O7—C6—C8123.66 (14)C14—C15—H15A112.6 (11)
O7—C6—C5120.62 (14)C16—C15—H15A108.1 (11)
C8—C6—C5115.67 (11)C14—C15—H15B109.2 (12)
C6—C8—C9109.94 (11)C16—C15—H15B108.9 (12)
C6—C8—H8A107.9 (13)H15A—C15—H15B106.8 (17)
C9—C8—H8A104.6 (13)C17—C16—C10108.88 (9)
C6—C8—H8B108.7 (15)C17—C16—C15109.91 (9)
C9—C8—H8B110.4 (15)C10—C16—C15108.80 (9)
H8A—C8—H8B115 (2)C17—C16—C598.12 (8)
C10—C9—C8109.26 (11)C10—C16—C5118.14 (9)
C10—C9—H9A108.6 (13)C15—C16—C5112.34 (9)
C8—C9—H9A109.0 (13)C18—C17—C3124.03 (10)
C10—C9—H9B104.8 (15)C18—C17—C16126.91 (10)
C8—C9—H9B113.6 (16)C3—C17—C16109.05 (9)
H9A—C9—H9B111.5 (19)C17—C18—C20115.70 (10)
C9—C10—C16111.81 (10)C17—C18—C19117.86 (10)
C9—C10—C11114.29 (10)C20—C18—C19126.32 (10)
C16—C10—C11106.27 (9)C18—C19—C11114.49 (9)
C9—C10—H10107.3 (11)C18—C19—H19A107.6 (14)
C16—C10—H10108.4 (11)C11—C19—H19A108.1 (15)
C11—C10—H10108.6 (12)C18—C19—H19B110.0 (16)
N12—C11—C10106.97 (10)C11—C19—H19B108.4 (16)
N12—C11—C19115.74 (11)H19A—C19—H19B108 (2)
C10—C11—C19113.10 (9)C21—C20—C18120.67 (11)
N12—C11—H11105.2 (11)C21—C20—H20118.9 (12)
C10—C11—H11107.5 (11)C18—C20—H20120.3 (12)
C19—C11—H11107.8 (12)C2—C21—C20122.43 (11)
C14—N12—C13110.99 (12)C2—C21—H21117.6 (11)
C14—N12—C11112.94 (9)C20—C21—H21119.8 (12)
C10—C11—N12—C13169.5 (2)

(II) (4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one .  Hydrogen-bond geometry (Å, º)

D—H···AD—HH···AD···AD—H···A
O1—H1···O4i0.84 (3)1.96 (3)2.791 (2)167 (3)

Symmetry code: (i) x+1/2, −y+3/2, −z+1.

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Articles from Acta Crystallographica Section E: Crystallographic Communications are provided here courtesy of International Union of Crystallography