Ozone → (S)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one

HRID 403580Notes

Reaction equation

HRID 403580 reaction equation
[CH2:1]([C@@:4]1([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:12])[CH2:6][CH2:5]1)[CH:2]=C.[O:24]=[O+][O-].[BH4-].[Na+]>C(Cl)Cl>[CH3:14][C:13]([CH3:15])([CH3:16])[C@@H:11]([N:7]1[CH2:6][CH2:5][C@@:4]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)([CH2:1][CH2:2][OH:24])[O:9][C:8]1=[O:10])[CH3:12]

Participants

5

Reactant 3

HCID 24823OzoneHCID 4311764Sodium borohydrideHCID 58485275(R)-6-allyl-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one

Product 1

HCID 58485265(S)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-oneYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-6-allyl-3-((2S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one [Isomer 1] (450 mg, 1.41 mmol) in dry CH2Cl2 (10 mL) was treated with O3 at −78° C. till the mixture turned blue. NaBH4 (157 mg, 4.23 mmol) was added, and the mixture was stirred at rt overnight. The solution was concentrated, and the residue was purified by preparative TLC followed by preparative HPLC to give (S)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one [Isomer 1] (265 mg, 58%). LC-MS Method 2 tR=3.83, min, m/z=669.03; 1H NMR (CDCl3): 0.71 (s, 9H), 1.06-1.11 (d, 3H), 2.07-2.19 (m, 2H), 2.31-2.28 (m, 1H), 2.67-2.76 (m, 1H), 3.12-3.18 (m, 1H), 3.47-3.58 (m, 1H), 3.69-3.78 (m, 1H), 4.38-4.47 (m, 1H), 7.03-7.09 (m, 2H), 7.26-7.33 (m, 2H).

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-3679a364043e4180846194fe0e37e65f
Source dataset
uspto-grants-2014_06
Patent number
US08748444B2

Reaction notes

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