(3S)-tert-butyl 3-((6S)-6-((2-methyloxiran-2-yl)methyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylate → (S)-tert-butyl 3-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylate

HRID 884356Notes

Reaction equation

HRID 884356 reaction equation
[CH3:1][C:2]1([CH2:5][C@@:6]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[O:11][C:10](=[O:12])[N:9]([C@H:13]3[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]3)[CH2:8][CH2:7]2)[CH2:4][O:3]1>C1COCC1>[OH:3][C:2]([CH3:4])([CH3:1])[CH2:5][C@@:6]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[O:11][C:10](=[O:12])[N:9]([C@H:13]2[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]2)[CH2:8][CH2:7]1

Participants

3

Reactant 1

HCID 58278664(3S)-tert-butyl 3-((6S)-6-((2-methyloxiran-2-yl)methyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylate

Product 1

HCID 58278660(S)-tert-butyl 3-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylateYield 19.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3S)-tert-butyl 3-((6S)-6-((2-methyloxiran-2-yl)methyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylate (2.87 g, 6.67 mmol) in dry THF (50 mL) was cooled to 0° C. After 20 min, the mixture was allowed to warm up to rt slowly. The mixture was stirred 2 h at rt, before being cooled to 0° C. again. The mixture was quenched with water (10 mL), 1% aq HCl (25 mL), diluted with EtOAc (120 mL). After separation, the organic layer was washed with brine (20 mL), dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 120 g silica gel column, eluted with a 50-100% EtOAc in hexanes gradient, to afford (S)-tert-butyl 3-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylate (0.55 g, 19% yield). LC-MS Method 1 tR=1.64 min., m/z 455 (M+Na).

Workup

  1. temperaturebefore being cooled to 0° C. again
  2. customThe mixture was quenched with water (10 mL), 1% aq HCl (25 mL)
  3. additiondiluted with EtOAc (120 mL)
  4. customAfter separation
  5. washthe organic layer was washed with brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by chromatography on a 120 g silica gel column
  9. washeluted with a 50-100% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-acbada64fe85476e8f5be55ad9952f99
Source dataset
uspto-grants-2012_08
Patent number
US08242111B2

Reaction notes

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