Acetic Acid → (1R,3S)-3-[2-phenyl-5-methyloxazol-4-ylmethoxy]cyclohexan-1-ol

HRID 10375Notes

Reaction equation

HRID 10375 reaction equation
[C:1]1([C:7]2[O:8][C:9]([CH3:21])=[C:10]([CH2:12][O:13][C@@H:14]3[CH2:19][CH2:18][CH2:17][C@H:16]([OH:20])[CH2:15]3)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[O-].[Na+].C(O)(=O)C>CO>[C:1]1([C:7]2[O:8][C:9]([CH3:21])=[C:10]([CH2:12][O:13][C@H:14]3[CH2:19][CH2:18][CH2:17][C@@H:16]([OH:20])[CH2:15]3)[N:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10942334Sodium MethoxideHCID 69539737(1S,3R)-3-[2-phenyl-5-methyloxazol-4-ylmethoxy]cyclohexan-1-ol

Product 1

HCID 58681951(1R,3S)-3-[2-phenyl-5-methyloxazol-4-ylmethoxy]cyclohexan-1-olYield 87.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

0.96 g of the (1R,3S)-acetyl compound from Example 20 was dissolved in approx. 5–10 ml of MeOH, admixed with 0.1 ml of NaOMe (30%) and stirred at 20–23° C. After 3 h, the mixture was neutralized with acetic acid and concentrated under reduced pressure, taken up with ethyl acetate, washed with saturated NaHCO3, dried (MgSO4) and concentrated under reduced pressure. After filtration through silica gel (10:1–0:1 n-heptane/ethyl acetate), 0.84 g of the desired (1R,3S)-3-[2-phenyl-5-methyloxazol-4-ylmethoxy]cyclohexan-1-ol having 95% ee (HPLC on Chiralpak AD 250×4.6; 1 ml/min, 25:1:0.5 heptane/EtOH/CH3CN+0.1% TFA) was obtained.

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed with saturated NaHCO3
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. filtrationAfter filtration through silica gel (10:1–0:1 n-heptane/ethyl acetate)

Sources & evidence

ORD record
ord-28284bcf97824fbea3f17da5d93ed400
Source dataset
uspto-grants-2006_08
Patent number
US07094795B2

Reaction notes

Loading…