Sodium hydride → 3-(1-(4-Bromophenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one

HRID 1422654Notes

Reaction equation

HRID 1422654 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([N:11]([CH2:16][CH2:17][C:18](O)([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:19][C:20]([CH3:22])=[CH2:21])[C:12](=[O:15])[O:13]C)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([N:11]3[CH2:16][CH2:17][C:18]([CH2:19][C:20]([CH3:22])=[CH2:21])([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[O:13][C:12]3=[O:15])[CH2:9][CH2:10]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 66870054Methyl 1-(4-bromophenyl)cyclopropyl(3-hydroxy-5-methyl-3-phenylhex-5-enyl)carbamate

Product 1

HCID 668695453-(1-(4-Bromophenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-oneYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 1-(4-bromophenyl)cyclopropyl(3-hydroxy-5-methyl-3-phenylhex-5-enyl)carbamate (58.8 mg, 0.129 mmol) in dry THF (10 mL) was added NaH (60% in mineral oil, 10 mg, 2 equiv). The mixture was heated to reflux for 2 h. LC-MS found the reaction was complete. The mixture was cooled to rt, quenched with satd aq NH4Cl (3 mL), diluted with EtOAc (30 mL), washed with 1% aq HCl (5 mL), satd aq NaHCO3 solution (5 mL) and brine (4 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 12-g silica gel column, eluted with a 0˜20% EtOAc in hexanes gradient, to afford 3-(1-(4-bromophenyl)cyclopropyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one (33.4 mg, 61%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 h
  3. customquenched with satd aq NH4Cl (3 mL)
  4. additiondiluted with EtOAc (30 mL)
  5. washwashed with 1% aq HCl (5 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by chromatography on a 12-g silica gel column
  9. washeluted with a 0˜20% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-9bc6237b0c464a93892e7d81be93087d
Source dataset
uspto-grants-2015_01
Patent number
US08927539B2

Reaction notes

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