Sodium hydride → (S)-tert-butyl 3-((R)-6-(2-methylallyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylate

HRID 884354Notes

Reaction equation

HRID 884354 reaction equation
O[C:2]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH2:23][C:24]([CH3:26])=[CH2:25])[CH2:3][CH2:4][N:5]([C:19]([O:21]C)=[O:20])[C@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1.[H-].[Na+]>C1COCC1.CCOCC>[CH3:26][C:24](=[CH2:25])[CH2:23][C@@:2]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:20][C:19](=[O:21])[N:5]([C@H:6]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 58278670(3S)-tert-butyl 3-((3-hydroxy-5-methyl-3-phenylhex-5-enyl)(methoxycarbonyl)amino)piperidine-1-carboxylate

Product 1

HCID 58278658(S)-tert-butyl 3-((R)-6-(2-methylallyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylateYield 55.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3S)-tert-butyl 3-((3-hydroxy-5-methyl-3-phenylhex-5-enyl)(methoxycarbonyl)amino)piperidine-1-carboxylate (5.80 g, 13 mmol) in dry THF (200 mL) was added NaH (60% in mineral oil, 1.04 g, 2 equiv). The mixture was heated to reflux for 2 h. After being cooled down to rt, the mixture was diluted with ether (200 mL), quenched with satd aq NH4Cl solution (25 mL), washed with 1% HCl solution (50 mL), brine (35 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 120 g silica gel column, eluted with a 40-70% EtOAc in hexanes gradient to afford (5)-tert-butyl 3-((R)-6-(2-methylallyI)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)piperidine-1-carboxylate (2.98 g, 55% yield). LC-MS Method 1 tR=1.92 min., m/z 437 (M+Na).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 h
  3. customquenched with satd aq NH4Cl solution (25 mL)
  4. washwashed with 1% HCl solution (50 mL), brine (35 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified by chromatography on a 120 g silica gel column
  8. washeluted with a 40-70% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-8134998660744174b34c66c2380a5f0b
Source dataset
uspto-grants-2012_08
Patent number
US08242111B2

Reaction notes

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