Imidazole → (-)-(1R,2S)-2-phenyl-1-cyclohexyl triisopropylsilyloxyacetate

HRID 2308240Notes

Reaction equation

HRID 2308240 reaction equation
C([O:8][CH2:9][C:10](Cl)=[O:11])C1C=CC=CC=1.[C:13]1([C@@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]2[OH:25])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH:26]([Si:29](Cl)([CH:33]([CH3:35])[CH3:34])[CH:30]([CH3:32])[CH3:31])([CH3:28])[CH3:27].N1C=CN=C1>CN(C)C=O.CCCCC>[OH:11][CH2:10][C:9]([O:25][C@@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][C@H:19]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:8].[CH:26]([Si:29]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[O:8][CH2:9][C:10]([O:25][C@@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][C@H:19]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:11])([CH3:28])[CH3:27]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 102793rel-(1R,2S)-2-PhenylcyclohexanolHCID 139400Triisopropylsilyl chlorideHCID 177085Benzyloxyacetyl chloride

Product 2

HCID 10000489(-)-(1R,2S)-2-phenyl-1-cyclohexyl triisopropylsilyloxyacetateYield 95%HCID 10059921(-)-(1R,2S)-2-phenyl-1-cyclohexyl hydroxyacetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8003PentaneSolvent

Procedure

A solution of (−)-(1R,2S)-2-phenyl-1-cyclohexyl hydroxyacetate (851 mg, 3.63 mmol) was prepared through esterification of benzyloxyacetyl chloride with (−)-(1R,2S)-2-phenyl-1-cyclohexanol followed by hydrogenolysis. Then, triisopropylsilyl chloride (840 mg, 4.36 mmol) and imidazole (618 mg, 9.08 mmol) in dimethylformamide (DMF) (1.7 mL) was added and stirred at room temperature for 12-20 hours. The mixture was poured into pentane (25 mL), and washed with water and brine. The combined organic layers were dried over anhydrous MgSO4 and concentrated in vacuo. The crude product was subjected to a purification on a short silica gel column using hexane/chloroform (3/1) as the eluant to give pure (−)-(1R,2S)-2-phenyl-1-cyclohexyl triisopropylsilyloxyacetate (1.35 g, 95% yield) as a colorless oil: [α]D20−17.1° C. 3.15, CHCl3); IR (neat) 1759, 1730 (nCO) cm−1; 1H NMR (CDCl3) δ0.93-0.99 (m, 21H), 1.30-1.62 (m, 4H), 1.72-2.0 (m, 3H), 2.10-2.19 (m, 1H), 2.66 (dt, J=11.5, 4.0 Hz, 1H), 3.90 (d, J=16.6 Hz, 1H), 4.07 (d, J=16.6 Hz, 1H), 5.07 (dt, J=10.6, 4.0 Hz, 1H), 7.16-7.30 (m, 5H). Anal. Calcd for C23H38O3Si: C, 70.72; H, 9.81. Found: C, 70.79; H, 9.85.

Workup

  1. washwashed with water and brine
  2. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was subjected to a purification on a short silica gel column

Sources & evidence

ORD record
ord-7598c42cec184549b2eae093aecb00ce
Source dataset
uspto-grants-2004_12
Patent number
US06835746B2

Reaction notes

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