Ozone → 6-(4-Fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one

HRID 2091514Notes

Reaction equation

HRID 2091514 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](C(C)(C)C)C)[CH2:6][CH2:5]1)[CH:2]=C.[O:24]=[O+][O-].[BH4-].[Na+]>C(Cl)Cl>[F:23][C:20]1[CH:21]=[CH:22][C:17]([C:4]2([CH2:1][CH2:2][OH:24])[O:9][C:8](=[O:10])[NH:7][CH2:6][CH2:5]2)=[CH:18][CH:19]=1

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 866587266-(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-40a8f55a2e514b70a5ab4b0b9c7c49bf
Source dataset
uspto-grants-2013_05
Patent number
US08440658B2

Reaction notes

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