Acetic Anhydride → (1R,3S)-3-[2-(4-fluorophenyl)oxazol4-ylmethoxy]cyclohexan-1-ol

HRID 10376Notes

Reaction equation

HRID 10376 reaction equation
C([O:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([O:11][CH2:12][C:13]2[N:14]=[C:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[O:16][CH:17]=2)[CH2:6]1)(=O)C.C(OC1CCCC(O)C1)C1C=CC=CC=1.C(OC(=O)C)(=O)C.C(OC1CCCC(OCC2C=CC=CC=2)C1)(=O)CCCC([O-])=O>P([O-])([O-])([O-])=O.COCCOC>[F:24][C:21]1[CH:20]=[CH:19][C:18]([C:15]2[O:16][CH:17]=[C:13]([CH2:12][O:11][C@H:7]3[CH2:8][CH2:9][CH2:10][C@@H:5]([OH:4])[CH2:6]3)[N:14]=2)=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 141727893-(Benzyloxy)cyclohexanolHCID 21980309HCID 21980309, compoundHCID 86594703Mono(3-benzyloxycyclohexyl) glutarate

Product 1

HCID 12113844(1R,3S)-3-[2-(4-fluorophenyl)oxazol4-ylmethoxy]cyclohexan-1-ol

Reagents, catalysts & solvents 2

HCID 1061PhosphateSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Approx. 10 mg of 3-[2-(4-fluorophenyl)oxazol-4-ylmethoxyl]cyclohexyl acetate (prepared by reacting 3-benzyloxycyclohexan-1-ol with acetic anhydride, in a similar manner to the synthesis of mono(3-benzyloxycyclohexyl) glutarate see Example 39) were taken up in 2 ml of phosphate buffer (0.1 M, pH=7.0) and 2 ml of DME and stirred with approx. 5 mg of Chirazyme L-2, lyo., at 20–23° C. for approx. 20–24 h. The reaction mixture was extracted with dichloromethane. The organic phase was admixed with toluene and concentrated by evaporation under reduced pressure. The determination of the optical purity for (1R,3S)-3-[2-(4-fluorophenyl)oxazol4-ylmethoxy]cyclohexan-1-ol gave 99.4% ee (HPLC on Chiralpak AD 250×4.6; 1 ml/min, acetonitrile) and 98.9% ee for the (1S,3R)-acetate (HPLC on Chiralcel OD 250×4.6; 1 ml/min, 110:5:1 heptane/EtOH/CH3CN+0.1% TFA).

Workup

  1. wait, at 20–23° C. for approx. 20–24 h
  2. extractionThe reaction mixture was extracted with dichloromethane
  3. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-bdea85ef300d4da788573db5b896a3b8
Source dataset
uspto-grants-2006_08
Patent number
US07094795B2

Reaction notes

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