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Acta Crystallogr Sect E Struct Rep Online. 2010 July 1; 66(Pt 7): o1623.
Published online 2010 June 16. doi:  10.1107/S1600536810017599
PMCID: PMC3006686

(2R*,6S*)-tert-Butyl 2,6-bis­(hydroxy­meth­yl)morpholine-4-carboxyl­ate

Abstract

In the title compound, C11H21NO5, the H atoms of the hydr­oxy groups are disordered over two positions, each in a 1:1 ratio. In the crystal, inter­molecular O—H(...)O hydrogen bonds link pairs of mol­ecules into centrosymmetric dimers. Weak inter­molecular O—H(...)O inter­actions further link these dimers into chains extended in the [100] direction.

Related literature

For details of the synthesis of 2,6-disubstituted morpholines, see: Dave & Sasaki (2004 [triangle]); Lupi et al. (2004 [triangle]).

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Object name is e-66-o1623-scheme1.jpg

Experimental

Crystal data

  • C11H21NO5
  • M r = 247.29
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1623-efi1.jpg
  • a = 21.909 (3) Å
  • b = 5.6643 (8) Å
  • c = 22.510 (3) Å
  • β = 107.612 (3)°
  • V = 2662.5 (7) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 293 K
  • 0.45 × 0.34 × 0.21 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • 6675 measured reflections
  • 2476 independent reflections
  • 1699 reflections with I > 2σ(I)
  • R int = 0.086

Refinement

  • R[F 2 > 2σ(F 2)] = 0.066
  • wR(F 2) = 0.199
  • S = 1.06
  • 2476 reflections
  • 173 parameters
  • 4 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.53 e Å−3
  • Δρmin = −0.38 e Å−3

Data collection: SMART (Bruker, 2002 [triangle]); cell refinement: SAINT (Bruker, 2002 [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: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810017599/cv2712sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810017599/cv2712Isup2.hkl

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

Acknowledgments

QC is indebted to Drs Liu Xuejun, Xie Jianshu and Shen Jingkang for supporting this project and for critical review of this manuscript. We gratefully acknowledge financial support from the Shanghai Pharmaceutical Group Co. Ltd. GX is grateful to the Shanghai Postdoctoral Sustentation Fund, China (grant No. 07R214213) for financial support.

supplementary crystallographic information

Comment

Morpholine and its derivatives have been widely investigated (Lupi et al., 2004; Dave &Sasaki, 2004) due to their importance in the search of new therapeutically and biologically active compounds. In the present paper, we report the crystal structure of the title compound, (I).

In (I) (Fig. 1), the H atoms of two hydroxy groups are disordered over two positions each in a ratio 1:1. In the crystal, intermolecular O—H···O hydrogen bonds (Table 1) link two molecules into centrosymmetric dimer. Weak intermolecular O—H···O interactions [O···O 3.269 (4) Å] (Table 1) link further these dimers into chains extended in direction [100].

Experimental

A mixture of (S)-(+)-benzyl glycidyl ether(9.84 g,60 mmol) and benzylamine(3.21 g,30 mmol) was heated with stirring at 60 centidegrees for 16 h. After being cooled to room temperature, an oil crude product (A) was obtained. Under ice-bath cooling, compound A (4.36 g,10 mmol) was dissolved in dry tetrahydrofuran (90 mL), 60% NaOH (1.0 g,25 mmol) was added over 15 minutes. The reaction mixture was stirred at 0 centidegrees for 30 minutes.Then a solution of TsCl(1.9 g,10 mmol) in dry THF(10 mL) was added dropwise over 30 minutes. After 10 min the solution was allowed to react at rt for 30 minutes and then heated at 50 centidegree until complete (usually about 2 h). After addition of an appropriate volume of 100 mL water, the aqueous layer was extracted three times with ethyl ether (30 mL). The combined organic layers were dried over anhydrous sodium sulfate and the solvent was removed and gave a yellow oil product(II). A solution of product II(2.09,5 mm mol) and acetic acid(10 mL) in methanol (30 mL) was treated with 10%Pd/C(200 mg) and then hydrogenated until complete(24 h). The catalyst was filtered and the solvent removed under reduced pressure.The pure product(III) was obtained. Product III was reacted with Boc anhydride to gave the target product. The target product was recrystallized from dry ether. Colourless crystals suitable for single crystal X-ray diffraction were obtained.

Refinement

H atoms bonded to O2 and O3 were each positioned in two possible idealized positions with occupancies fixed to 0.5, and were isotropically refined with the O—H bond length restrained to 0.82 (3) Å. C-bound H atoms were geometrically positioned (C—H = 0.96-0.98 Å) and treated as riding, with Uiso(H)=1.2-1.5 Ueq(C).

Figures

Fig. 1.
The molecular structure of (I) showing the atomic numbering and 30% probability displacement ellipsoids. For each of two disordered H atoms (bound to O2 and O3) only one position is shown.

Crystal data

C11H21NO5F(000) = 1072
Mr = 247.29Dx = 1.234 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
a = 21.909 (3) ÅCell parameters from 1734 reflections
b = 5.6643 (8) Åθ = 4.6–44.5°
c = 22.510 (3) ŵ = 0.10 mm1
β = 107.612 (3)°T = 293 K
V = 2662.5 (7) Å3Prismatic, colourless
Z = 80.45 × 0.34 × 0.21 mm

Data collection

Bruker SMART CCD area-detector diffractometer1699 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.086
graphiteθmax = 25.5°, θmin = 1.9°
[var phi] and ω scansh = −26→25
6675 measured reflectionsk = −6→6
2476 independent reflectionsl = −27→19

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)] = 0.066Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.199H atoms treated by a mixture of independent and constrained refinement
S = 1.06w = 1/[σ2(Fo2) + (0.0978P)2 + 0.9544P] where P = (Fo2 + 2Fc2)/3
2476 reflections(Δ/σ)max = 0.028
173 parametersΔρmax = 0.53 e Å3
4 restraintsΔρmin = −0.38 e Å3

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.
Refinement. 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. 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*/UeqOcc. (<1)
O10.41734 (8)1.2127 (3)0.00900 (7)0.0487 (5)
O20.33480 (10)1.4453 (4)−0.09361 (9)0.0668 (6)
O30.53146 (9)1.4619 (4)0.06357 (9)0.0638 (6)
O40.28864 (15)0.7185 (5)0.10144 (10)0.1312 (14)
O50.38194 (9)0.7747 (3)0.17686 (8)0.0598 (6)
N10.36921 (10)0.9179 (4)0.08274 (10)0.0584 (6)
C10.34976 (12)1.1868 (5)−0.00456 (11)0.0503 (7)
H10.33351.30980.01720.060*
C20.33469 (15)0.9479 (5)0.01673 (12)0.0650 (8)
H2A0.28900.93440.01020.078*
H2B0.34720.8254−0.00740.078*
C30.43769 (13)0.9642 (5)0.09948 (13)0.0622 (8)
H3A0.45840.84010.08290.075*
H3B0.45580.96430.14450.075*
C40.44998 (11)1.1985 (4)0.07397 (10)0.0477 (6)
H40.43481.32510.09560.057*
C50.32122 (14)1.2194 (5)−0.07387 (12)0.0623 (8)
H5A0.33811.0993−0.09530.075*
H5B0.27521.1985−0.08510.075*
C60.51984 (12)1.2342 (5)0.08203 (12)0.0566 (7)
H6A0.54421.21030.12540.068*
H6B0.53411.11850.05730.068*
C70.34176 (15)0.7944 (5)0.11901 (12)0.0621 (8)
C80.36300 (13)0.6503 (5)0.22584 (11)0.0527 (7)
C90.30285 (16)0.7518 (6)0.23374 (18)0.0880 (11)
H9A0.30610.92080.23580.132*
H9B0.29680.69260.27150.132*
H9C0.26700.70710.19890.132*
C100.3569 (2)0.3929 (6)0.21181 (18)0.1117 (15)
H10A0.32110.36620.17530.168*
H10B0.35030.30980.24650.168*
H10C0.39530.33670.20450.168*
C110.41842 (16)0.7042 (7)0.28251 (14)0.0860 (11)
H11A0.45700.63920.27730.129*
H11B0.41080.63570.31860.129*
H11C0.42300.87210.28780.129*
H2E0.3751 (10)1.474 (9)−0.083 (2)0.050 (15)*0.50
H3E0.5706 (11)1.495 (9)0.074 (3)0.056 (16)*0.50
H2D0.303 (2)1.529 (11)−0.104 (3)0.09 (3)*0.50
H3D0.507 (2)1.477 (10)0.0285 (13)0.055 (16)*0.50

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0563 (11)0.0596 (11)0.0309 (9)−0.0055 (8)0.0143 (8)0.0060 (7)
O20.0609 (14)0.0802 (15)0.0548 (12)−0.0088 (12)0.0109 (11)0.0241 (11)
O30.0524 (12)0.0870 (15)0.0460 (12)−0.0197 (10)0.0059 (10)0.0093 (10)
O40.147 (2)0.169 (3)0.0511 (13)−0.123 (2)−0.0095 (14)0.0263 (15)
O50.0710 (12)0.0721 (12)0.0389 (10)−0.0173 (9)0.0205 (9)0.0112 (8)
N10.0625 (14)0.0725 (15)0.0412 (12)−0.0083 (11)0.0172 (10)0.0176 (11)
C10.0550 (15)0.0575 (16)0.0366 (13)−0.0072 (12)0.0113 (12)0.0049 (11)
C20.083 (2)0.0706 (19)0.0403 (15)−0.0186 (15)0.0171 (14)0.0078 (13)
C30.0615 (17)0.0780 (19)0.0519 (16)0.0106 (14)0.0243 (14)0.0236 (14)
C40.0539 (15)0.0601 (15)0.0305 (12)0.0048 (11)0.0149 (11)0.0068 (11)
C50.0687 (17)0.0713 (18)0.0415 (15)−0.0159 (14)0.0084 (13)0.0121 (13)
C60.0551 (16)0.0737 (19)0.0406 (14)0.0023 (13)0.0143 (12)0.0147 (13)
C70.086 (2)0.0583 (16)0.0398 (15)−0.0304 (15)0.0167 (14)0.0014 (12)
C80.0714 (17)0.0535 (15)0.0382 (14)−0.0117 (12)0.0242 (13)0.0085 (11)
C90.084 (2)0.101 (3)0.096 (3)−0.0023 (18)0.053 (2)0.019 (2)
C100.212 (5)0.0526 (19)0.087 (3)−0.011 (2)0.070 (3)0.0050 (19)
C110.087 (2)0.119 (3)0.0514 (18)−0.0166 (19)0.0197 (17)0.0188 (18)

Geometric parameters (Å, °)

O1—C41.422 (3)C3—H3A0.9700
O1—C11.426 (3)C3—H3B0.9700
O2—C51.415 (3)C4—C61.499 (3)
O2—H2E0.858 (19)C4—H40.9800
O2—H2D0.82 (2)C5—H5A0.9700
O3—C61.402 (3)C5—H5B0.9700
O3—H3E0.84 (2)C6—H6A0.9700
O3—H3D0.817 (19)C6—H6B0.9700
O4—C71.191 (4)C8—C101.489 (4)
O5—C71.338 (3)C8—C91.497 (4)
O5—C81.470 (3)C8—C111.503 (4)
N1—C71.347 (3)C9—H9A0.9600
N1—C31.456 (3)C9—H9B0.9600
N1—C21.459 (3)C9—H9C0.9600
C1—C21.505 (4)C10—H10A0.9600
C1—C51.506 (3)C10—H10B0.9600
C1—H10.9800C10—H10C0.9600
C2—H2A0.9700C11—H11A0.9600
C2—H2B0.9700C11—H11B0.9600
C3—C41.502 (4)C11—H11C0.9600
C4—O1—C1112.38 (18)C1—C5—H5A109.2
C5—O2—H2E112 (3)O2—C5—H5B109.2
C5—O2—H2D112 (5)C1—C5—H5B109.2
H2E—O2—H2D134 (6)H5A—C5—H5B107.9
C6—O3—H3E113 (4)O3—C6—C4111.0 (2)
C6—O3—H3D105 (4)O3—C6—H6A109.4
H3E—O3—H3D125 (6)C4—C6—H6A109.4
C7—O5—C8121.21 (19)O3—C6—H6B109.4
C7—N1—C3123.4 (2)C4—C6—H6B109.4
C7—N1—C2119.3 (2)H6A—C6—H6B108.0
C3—N1—C2114.8 (2)O4—C7—O5125.6 (2)
O1—C1—C2109.8 (2)O4—C7—N1123.9 (3)
O1—C1—C5106.7 (2)O5—C7—N1110.5 (2)
C2—C1—C5112.2 (2)O5—C8—C10109.7 (2)
O1—C1—H1109.4O5—C8—C9111.3 (2)
C2—C1—H1109.4C10—C8—C9112.0 (3)
C5—C1—H1109.4O5—C8—C11101.6 (2)
N1—C2—C1109.5 (2)C10—C8—C11112.1 (3)
N1—C2—H2A109.8C9—C8—C11109.6 (3)
C1—C2—H2A109.8C8—C9—H9A109.5
N1—C2—H2B109.8C8—C9—H9B109.5
C1—C2—H2B109.8H9A—C9—H9B109.5
H2A—C2—H2B108.2C8—C9—H9C109.5
N1—C3—C4110.5 (2)H9A—C9—H9C109.5
N1—C3—H3A109.5H9B—C9—H9C109.5
C4—C3—H3A109.6C8—C10—H10A109.5
N1—C3—H3B109.6C8—C10—H10B109.5
C4—C3—H3B109.5H10A—C10—H10B109.5
H3A—C3—H3B108.1C8—C10—H10C109.5
O1—C4—C6107.10 (19)H10A—C10—H10C109.5
O1—C4—C3110.5 (2)H10B—C10—H10C109.5
C6—C4—C3111.5 (2)C8—C11—H11A109.5
O1—C4—H4109.2C8—C11—H11B109.5
C6—C4—H4109.2H11A—C11—H11B109.5
C3—C4—H4109.2C8—C11—H11C109.5
O2—C5—C1112.0 (2)H11A—C11—H11C109.5
O2—C5—H5A109.2H11B—C11—H11C109.5
C4—O1—C1—C2−61.4 (3)C2—C1—C5—O2179.3 (2)
C4—O1—C1—C5176.8 (2)O1—C4—C6—O364.6 (3)
C7—N1—C2—C1145.5 (3)C3—C4—C6—O3−174.3 (2)
C3—N1—C2—C1−52.0 (3)C8—O5—C7—O40.4 (5)
O1—C1—C2—N155.4 (3)C8—O5—C7—N1179.1 (2)
C5—C1—C2—N1173.9 (2)C3—N1—C7—O4−165.7 (3)
C7—N1—C3—C4−147.9 (3)C2—N1—C7—O4−4.8 (5)
C2—N1—C3—C450.5 (3)C3—N1—C7—O515.6 (4)
C1—O1—C4—C6−178.62 (19)C2—N1—C7—O5176.5 (2)
C1—O1—C4—C359.7 (3)C7—O5—C8—C1068.9 (4)
N1—C3—C4—O1−52.3 (3)C7—O5—C8—C9−55.7 (3)
N1—C3—C4—C6−171.3 (2)C7—O5—C8—C11−172.3 (3)
O1—C1—C5—O2−60.5 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O3—H3D···O3i0.82 (3)2.02 (3)2.809 (4)164 (6)
O2—H2E···O3i0.86 (3)1.99 (3)2.849 (3)176 (5)
O2—H2D···O4ii0.82 (4)2.48 (5)3.269 (4)163 (6)

Symmetry codes: (i) −x+1, −y+3, −z; (ii) −x+1/2, −y+5/2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CV2712).

References

  • Bruker (2002). SMART and SAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • Dave, R. & Sasaki, N. A. (2004). Org. Lett.6, 15–18. [PubMed]
  • Lupi, V., Albanese, D., Landini, D., Scaletti, D. & Penso, M. (2004). Tetrahedron, 60, 11709–11718.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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