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Acta Crystallogr Sect E Struct Rep Online. 2010 December 1; 66(Pt 12): o3105.
Published online 2010 November 6. doi:  10.1107/S1600536810044909
PMCID: PMC3011791

(1R,3S)-Methyl 6,7-dimeth­oxy-1-(4-meth­oxy­phen­yl)-1,2,3,4-tetra­hydro­isoquinoline-3-carboxyl­ate

Abstract

The title compound, C20H23NO5, is the third in a series of tetra­hydoisoquinoline (TIQ) compounds that are precursors to novel chiral catalysts. The N-containing six-membered ring assumes a half-boat conformation. No hydrogen bonding is observed in the crystal structure.

Related literature

For related structures, see: Naicker et al. (2009 [triangle], 2010 [triangle]); Alberach et al. (2004 [triangle]). For the synthesis of the title compound, see: Aubry et al. (2006 [triangle]).

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Object name is e-66-o3105-scheme1.jpg

Experimental

Crystal data

  • C20H23NO5
  • M r = 357.39
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o3105-efi1.jpg
  • a = 5.3719 (7) Å
  • b = 12.1726 (14) Å
  • c = 27.021 (3) Å
  • V = 1766.9 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 173 K
  • 0.20 × 0.12 × 0.12 mm

Data collection

  • Bruker Kappa DUO APEXII diffractometer
  • 13619 measured reflections
  • 2878 independent reflections
  • 2538 reflections with I > 2σ(I)
  • R int = 0.032

Refinement

  • R[F 2 > 2σ(F 2)] = 0.036
  • wR(F 2) = 0.090
  • S = 1.04
  • 2878 reflections
  • 239 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.26 e Å−3
  • Δρmin = −0.18 e Å−3

Data collection: APEX2 (Bruker, 2006 [triangle]); cell refinement: SAINT (Bruker, 2006 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: OLEX2 (Dolomanov et al., 2009 [triangle]); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810044909/hg2711sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810044909/hg2711Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors thank Dr Hong Su of the University of Capetown for the data collection and structure refinement.

supplementary crystallographic information

Comment

The title compound was derived from commercially available L-DOPA and anisaldehyde. Diastereomers formed during the first step of the synthesis were separated to yield subsequent derivatives and the title compound with the stereochemistry as illustrated in Fig. 1. The title compound is the third report in a series of molecules containing a tetrahydroisoquinoline backbone and is a precursor to one of the molecules that we previously reported ((1R,3S)-methyl 2-benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate), (Naicker et al., 2009). The molecule has been reported previously and the absolute stereochemistry of the diastereomer was confirmed to be R,S at C4 and C2 positions respectively by proton NMR (Aubry et al., 2006).

There are a number of common features found in this structure and that of the the unprotected secondary amine system. First, the N-containing six membered ring assumes a half boat conformation. This differs from last report for the (1R,3S)-2-benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4 tetrahydroisoquinolin-3-yl diphenylmethanol structure (Naicker et al., 2010) and previous reports by Alberach et al. (2004) and Aubry et al. (2006) where the heteroatomic ring adopted a half chair conformation. Second, given the presence of the secondary amine, ether and in this example ester functional groups, no hydrogen bonding is observed in any of the structures of this series, (see Fig. 2).

Experimental

A solution of the Cbz protected trans-6,7-dimethoxy-1-(4-methoxyphenyl)-TIQ methyl ester (1.0 g, 0.21 mmol) in THF (20 ml) was added to a suspension of activated 10 wt% Pd/C (500 mg) in dry MeOH (20 ml). The mixture was connected to a hydrogen source at one atmosphere and stirred at room temperature for 1 h. Completion of the reaction was monitored through TLC in hexane/ethyl acetate (50/50, Rf = 0.6). The Pd/C was filtered through a Celite pad and washed with methanol (20 ml). The filtrate was evaporated under reduced pressure affording the crude amino ester, which was purified by column chromatography using ethyl acetate/hexane (50:50) as the eluent to yield pure title compound (0.70 g, 93%) as a yellow solid. m.p. = 392–393 K. Crystals suitable for X-ray diffraction were obtained by slow evaporation of the title compound in MeOH at room temperature.

1H NMR (600 MHz, CdCl3, d, p.p.m.): 1.58 (broad s, 1H), 2.99 (dd, 1H), 3.09 (dd, 1H), 3.60 (s, 3H), 3.66 (s, 3H) 3.67(s, 3H), 3.78 (m, 1H), 3.88 (s, 3H), 5.23 (s, 1H), 6.30(s, 1H), 6.61 (s, 1H), 6.82 (d, 2H), 7.09 (d, 2H).

IR: 2946 (w), 1700 (w), 1507 (s), 1223 (vs), 832 (s), 563 (w)

Refinement

All H atoms, except H1N, were positioned geometrically with C—H distances ranging from 0.95 Å to 1.00 Å and refined as riding on their parent atoms, with Uiso (H) = 1.2–1.5Ueq (C).

Figures

Fig. 1.
The title compound (all H atoms omitted for clarity). All non-H atoms are shown as ellipsoids with probability level of 50%.
Fig. 2.
Projection viewed along [010].

Crystal data

C20H23NO5F(000) = 760
Mr = 357.39Dx = 1.344 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 13619 reflections
a = 5.3719 (7) Åθ = 2.3–29.6°
b = 12.1726 (14) ŵ = 0.10 mm1
c = 27.021 (3) ÅT = 173 K
V = 1766.9 (4) Å3Needle, colourless
Z = 40.20 × 0.12 × 0.12 mm

Data collection

Bruker Kappa DUO APEXII diffractometer2538 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.032
graphiteθmax = 29.6°, θmin = 2.3°
0.5° [var phi] scans and ω scansh = −7→7
13619 measured reflectionsk = −16→16
2878 independent reflectionsl = −26→37

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.090H atoms treated by a mixture of independent and constrained refinement
S = 1.04w = 1/[σ2(Fo2) + (0.0435P)2 + 0.3587P] where P = (Fo2 + 2Fc2)/3
2878 reflections(Δ/σ)max = 0.001
239 parametersΔρmax = 0.26 e Å3
1 restraintΔρmin = −0.18 e Å3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C10.3734 (3)0.44954 (13)0.76583 (6)0.0498 (4)
H1A0.2473 (3)0.28121 (11)0.78678 (5)0.0378 (3)
H1B0.4011 (3)0.34146 (11)1.09674 (5)0.0307 (3)
C20.3315 (3)0.91415 (10)0.85890 (5)0.0351 (3)
H20.6521 (3)0.82927 (10)0.91879 (5)0.0334 (3)
C40.0808 (3)0.40422 (12)0.87542 (5)0.0253 (3)
H40.078 (4)0.3258 (5)0.8806 (7)0.031 (5)*
C5−0.0280 (3)0.55050 (15)0.81826 (7)0.0269 (4)
C6−0.01840.57130.78290.032*
H6−0.19970.56520.82980.032*
C70.0265 (3)0.42813 (14)0.82338 (6)0.0264 (4)
C8−0.12790.38710.81410.032*
C90.3147 (3)0.45361 (13)0.89317 (6)0.0224 (3)
H90.45740.41900.87520.027*
C100.3126 (3)0.57639 (13)0.88213 (6)0.0211 (3)
C110.4841 (3)0.64470 (14)0.90671 (6)0.0229 (3)
C120.59670.61360.92990.027*
H12A0.4912 (3)0.75648 (14)0.89759 (6)0.0242 (3)
H12B0.3187 (4)0.80245 (13)0.86413 (6)0.0250 (3)
H12C0.1543 (3)0.73469 (14)0.83937 (6)0.0253 (3)
C130.04070.76570.81640.030*
C140.1519 (3)0.62062 (14)0.84759 (6)0.0231 (3)
H140.2348 (4)0.39131 (15)0.78851 (6)0.0276 (4)
C150.4358 (4)0.23681 (18)0.75419 (8)0.0383 (5)
H150.43040.15640.75530.057*
C160.60030.26230.76490.057*
C170.40440.26170.72030.057*
H170.3392 (3)0.42874 (12)0.94812 (6)0.0216 (3)
C180.5433 (3)0.37117 (13)0.96620 (6)0.0239 (3)
H180.67270.35010.94420.029*
C190.5606 (3)0.34403 (14)1.01604 (7)0.0256 (3)
H19A0.70070.30451.02800.031*
H19B0.3716 (3)0.37499 (13)1.04827 (6)0.0238 (3)
H19C0.1682 (3)0.43478 (13)1.03116 (6)0.0250 (3)
C200.04060.45741.05330.030*
H20A0.1551 (3)0.46090 (13)0.98113 (6)0.0245 (3)
H20B0.01670.50170.96920.029*
H20C0.1949 (4)0.35863 (18)1.12932 (7)0.0399 (5)
C210.23740.33191.16250.060*
H21A0.04960.31851.11690.060*
H21B0.15640.43721.13090.060*
H21C0.8323 (4)0.78695 (16)0.95244 (7)0.0317 (4)
N10.93530.84730.96500.047*
H1N0.93800.73350.93530.047*
O10.74740.75100.98020.047*
O20.1569 (4)0.96322 (17)0.82600 (8)0.0419 (5)
O30.18351.04290.82520.063*
O4−0.01250.94770.83750.063*
O50.17970.93290.79270.063*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0537 (10)0.0375 (8)0.0581 (10)−0.0089 (8)0.0274 (9)−0.0036 (7)
H1A0.0463 (8)0.0301 (7)0.0370 (7)−0.0025 (6)0.0121 (7)−0.0065 (6)
H1B0.0360 (7)0.0309 (6)0.0252 (6)0.0054 (6)0.0012 (5)0.0018 (5)
C20.0433 (8)0.0212 (6)0.0409 (8)−0.0014 (6)−0.0095 (7)0.0042 (5)
H20.0349 (7)0.0253 (6)0.0399 (7)−0.0042 (6)−0.0127 (6)−0.0019 (5)
C40.0265 (7)0.0241 (7)0.0253 (7)−0.0065 (6)0.0018 (6)−0.0012 (6)
C50.0242 (8)0.0296 (8)0.0269 (8)−0.0021 (7)−0.0041 (7)−0.0024 (7)
C70.0256 (8)0.0276 (8)0.0261 (8)−0.0063 (7)0.0012 (7)−0.0034 (7)
C90.0226 (7)0.0205 (7)0.0242 (7)−0.0020 (6)0.0033 (6)−0.0014 (6)
C100.0214 (7)0.0201 (7)0.0218 (7)−0.0015 (6)0.0032 (6)−0.0004 (6)
C110.0221 (7)0.0237 (7)0.0229 (7)0.0002 (6)−0.0005 (6)0.0009 (6)
H12A0.0246 (8)0.0236 (7)0.0246 (8)−0.0022 (7)−0.0007 (7)−0.0023 (6)
H12B0.0292 (8)0.0207 (7)0.0252 (8)−0.0003 (7)0.0020 (7)0.0014 (6)
H12C0.0256 (8)0.0268 (8)0.0235 (8)0.0008 (7)−0.0023 (7)0.0023 (6)
C140.0229 (7)0.0254 (7)0.0211 (7)−0.0019 (7)0.0015 (7)−0.0027 (6)
H140.0302 (9)0.0302 (9)0.0223 (8)−0.0047 (7)−0.0004 (7)−0.0057 (7)
C150.0400 (11)0.0407 (11)0.0342 (10)0.0036 (9)0.0033 (9)−0.0115 (9)
H170.0226 (7)0.0175 (7)0.0248 (8)−0.0022 (6)0.0006 (7)−0.0006 (6)
C180.0198 (7)0.0214 (7)0.0304 (8)0.0000 (6)0.0042 (7)−0.0027 (6)
C190.0214 (7)0.0225 (7)0.0329 (9)0.0021 (6)−0.0017 (7)0.0004 (7)
H19B0.0281 (8)0.0185 (7)0.0247 (8)−0.0027 (6)−0.0004 (7)−0.0006 (6)
H19C0.0252 (7)0.0220 (7)0.0278 (8)0.0027 (7)0.0041 (7)−0.0028 (6)
H20A0.0235 (7)0.0211 (7)0.0289 (8)0.0036 (7)0.0012 (7)0.0006 (6)
H20C0.0469 (12)0.0432 (11)0.0296 (9)0.0033 (10)0.0082 (9)0.0042 (8)
H21C0.0302 (9)0.0348 (9)0.0300 (9)−0.0043 (8)−0.0062 (8)−0.0030 (7)
O20.0488 (12)0.0272 (9)0.0498 (12)0.0069 (10)−0.0084 (11)0.0058 (8)

Geometric parameters (Å, °)

C1—H141.197 (2)H12B—H12C1.381 (2)
H1A—H141.343 (2)H12C—C130.9500
H1A—C151.446 (2)H12C—C141.406 (2)
H1B—H19B1.381 (2)C15—H150.9800
H1B—H20C1.430 (2)C15—C160.9800
C2—H12B1.369 (2)C15—C170.9800
C2—O21.424 (2)H17—C181.390 (2)
H2—H12A1.364 (2)H17—H20A1.388 (2)
H2—H21C1.425 (2)C18—H180.9500
C4—H40.965 (5)C18—C191.390 (2)
C4—C71.465 (2)C19—H19A0.9500
C4—C91.473 (2)C19—H19B1.390 (2)
C5—C60.9900H19B—H19C1.392 (2)
C5—H60.9900H19C—C200.9500
C5—C71.524 (3)H19C—H20A1.391 (2)
C5—C141.514 (2)H20A—H20B0.9500
C7—C81.0000H20C—C210.9800
C7—H141.530 (3)H20C—H21A0.9800
C9—H91.0000H20C—H21B0.9800
C9—C101.524 (2)H21C—N10.9800
C9—H171.521 (2)H21C—H1N0.9800
C10—C111.407 (2)H21C—O10.9800
C10—C141.381 (2)O2—O30.9800
C11—C120.9500O2—O40.9800
C11—H12A1.383 (2)O2—O50.9800
H12A—H12B1.410 (2)
C1—H14—H1A122.83 (18)H12B—C2—O2116.62 (16)
C1—H14—C7126.64 (17)H12B—H12C—C13119.4
H1A—H14—C7110.53 (15)H12B—H12C—C14121.27 (16)
H1A—C15—H15109.5H12C—H12B—H12A119.57 (15)
H1A—C15—C16109.5H12C—C14—C5118.69 (16)
H1A—C15—C17109.5C14—C5—C6109.1
H1B—H19B—C19115.50 (16)C14—C5—H6109.1
H1B—H19B—H19C124.03 (16)C14—C5—C7112.38 (15)
H1B—H20C—C21109.5C14—C10—C9121.29 (15)
H1B—H20C—H21A109.5C14—C10—C11119.86 (15)
H1B—H20C—H21B109.5C14—H12C—C13119.4
C2—H12B—H12A115.30 (16)H14—H1A—C15115.43 (16)
C2—H12B—H12C125.13 (16)H14—C7—C8107.8
C2—O2—O3109.5H15—C15—C16109.5
C2—O2—O4109.5H15—C15—C17109.5
C2—O2—O5109.5C16—C15—C17109.5
H2—H12A—C11125.56 (16)H17—C9—H9108.9
H2—H12A—H12B115.32 (15)H17—C9—C10112.76 (13)
H2—H21C—N1109.5H17—C18—H18119.6
H2—H21C—H1N109.5H17—H20A—H19C121.60 (16)
H2—H21C—O1109.5H17—H20A—H20B119.2
C4—C7—C5108.63 (14)C18—H17—C9120.77 (15)
C4—C7—C8107.8C18—C19—H19A120.2
C4—C7—H14112.79 (15)C19—C18—H17120.87 (16)
C4—C9—H9108.9C19—C18—H18119.6
C4—C9—C10109.28 (14)C19—H19B—H19C120.46 (16)
C4—C9—H17108.07 (13)H19B—H1B—H20C116.85 (15)
C5—C7—C8107.8H19B—C19—C18119.62 (16)
C5—C7—H14111.78 (15)H19B—C19—H19A120.2
C6—C5—H6107.9H19B—H19C—C20120.6
C7—C4—H4109.5 (12)H19C—H20A—H20B119.2
C7—C4—C9113.65 (13)H20A—H17—C9120.63 (15)
C7—C5—C6109.1H20A—H17—C18118.58 (15)
C7—C5—H6109.1H20A—H19C—H19B118.84 (16)
C9—C4—H4111.7 (13)H20A—H19C—C20120.6
C10—C9—H9108.9C21—H20C—H21A109.5
C10—C11—C12119.5C21—H20C—H21B109.5
C10—C14—C5122.23 (15)H21A—H20C—H21B109.5
C10—C14—H12C119.08 (16)N1—H21C—H1N109.5
C11—C10—C9118.82 (15)N1—H21C—O1109.5
C11—H12A—H12B119.11 (16)H1N—H21C—O1109.5
H12A—H2—H21C117.63 (14)O3—O2—O4109.5
H12A—C11—C10121.00 (16)O3—O2—O5109.5
H12A—C11—C12119.5O4—O2—O5109.5
H1B—H19B—H19C—H20A−177.95 (16)C11—C10—C14—C5177.06 (15)
C2—H12B—H12C—C14−179.09 (17)C11—C10—C14—H12C−3.2 (2)
H2—H12A—H12B—C2−2.1 (2)C11—H12A—H12B—C2177.27 (16)
H2—H12A—H12B—H12C177.55 (16)C11—H12A—H12B—H12C−3.1 (3)
C4—C7—H14—C1−110.1 (2)H12A—H12B—H12C—C141.3 (3)
C4—C7—H14—H1A68.92 (19)H12B—H12C—C14—C5−178.36 (16)
C4—C9—C10—C11163.71 (14)H12B—H12C—C14—C101.9 (3)
C4—C9—C10—C14−18.3 (2)C14—C5—C7—C443.2 (2)
C4—C9—H17—C18121.18 (16)C14—C5—C7—H14−81.93 (18)
C4—C9—H17—H20A−57.33 (19)C14—C10—C11—H12A1.4 (2)
C5—C7—H14—C112.7 (3)C15—H1A—H14—C1−1.9 (3)
C5—C7—H14—H1A−168.34 (16)C15—H1A—H14—C7179.03 (15)
C7—C4—C9—C1053.33 (17)H17—C9—C10—C1143.5 (2)
C7—C4—C9—H17176.36 (14)H17—C9—C10—C14−138.55 (16)
C7—C5—C14—C10−11.8 (2)H17—C18—C19—H19B−0.1 (3)
C7—C5—C14—H12C168.42 (16)C18—H17—H20A—H19C−1.4 (2)
C9—C4—C7—C5−67.42 (18)C18—C19—H19B—H1B178.05 (15)
C9—C4—C7—H1457.07 (19)C18—C19—H19B—H19C−1.3 (2)
C9—C10—C11—H12A179.36 (15)C19—H19B—H19C—H20A1.3 (2)
C9—C10—C14—C5−0.9 (2)H19B—H19C—H20A—H170.0 (3)
C9—C10—C14—H12C178.92 (15)H20A—H17—C18—C191.5 (2)
C9—H17—C18—C19−177.06 (15)H20C—H1B—H19B—C19−171.63 (16)
C9—H17—H20A—H19C177.10 (15)H20C—H1B—H19B—H19C7.7 (2)
C10—C9—H17—C18−117.93 (17)H21C—H2—H12A—C111.4 (3)
C10—C9—H17—H20A63.6 (2)H21C—H2—H12A—H12B−179.25 (15)
C10—C11—H12A—H2−178.92 (16)O2—C2—H12B—H12A−178.97 (16)
C10—C11—H12A—H12B1.8 (3)O2—C2—H12B—H12C1.4 (3)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2711).

References

  • Alberach, L., Bailey, P. D., Clingan, P. D., Mills, T. J., Price, R. A. & Pritchard, R. G. (2004). Eur. J. Org. Chem.9, 1887–1890.
  • Aubry, S., Pellet-Rostaing, S., Faure, R. & Lemaire, M. (2006). J. Heterocycl. Chem.43, 139–148.
  • Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
  • Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst.42, 339–341.
  • Naicker, T., Govender, T., Kruger, H. G. & Maguire, G. E. M. (2010). Acta Cryst. E66, o638. [PMC free article] [PubMed]
  • Naicker, T., McKay, M., Govender, T., Kruger, H. G. & Maguire, G. E. M. (2009). Acta Cryst. E65, o3278. [PMC free article] [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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