(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-oxopropyl)-6-phenyl-1,3-oxazinan-2-one → 6-(2-Hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one
Reaction equation
BrC1C=CC([C@@H]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23](=[O:25])[CH3:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:26])C)=CC=1.[CH3:27][Mg]Br>C1COCC1>[OH:25][C:23]([CH3:24])([CH3:27])[CH2:22][C:13]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[O:12][C:11](=[O:26])[NH:10][CH2:15][CH2:14]1Participants
4
Procedure
To a solution of (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-oxopropyl)-6-phenyl -1,3-oxazinan-2-one (12 g, 28.8 mmol) in anhydrous THF (100 mL) was added dropwise methylmagnesium bromide (48 mL, 144 mmol) at −78° C. under nitrogen. The mixture was stirred at rt for 1 h. The reaction mixture was quenched with aqueous NH4Cl solution (50 mL) in ice water bath. The layers were separated and the aqueous layer was extracted with EtOAc (150 mL). The combined organic phases were washed with brine (30 mL), dried over Na2SO4 and concentrated in vacuo to give the crude product, which was purified by preparative HPLC and chiral HPLC to afford (S)-3-(S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (6.6 g, 53%).
Workup
- customThe reaction mixture was quenched with aqueous NH4Cl solution (50 mL) in ice water bath
- customThe layers were separated
- extractionthe aqueous layer was extracted with EtOAc (150 mL)
- washThe combined organic phases were washed with brine (30 mL)
- dry with materialdried over Na2SO4
- concentrationconcentrated in vacuo
- customto give the crude product, which
- customwas purified by preparative HPLC and chiral HPLC
Sources & evidence
- ORD record
- ord-8f6886dbad314d3dbb552f394af4316b
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08114868B2
Reaction notes
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