Sodium hydride → (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one

HRID 2037791Notes

Reaction equation

HRID 2037791 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]([CH2:15][CH2:16][C:17]([OH:28])([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:18][C:19]([CH3:21])=[CH2:20])[C:11](=O)[O:12]C)[CH3:9])=[CH:4][CH:3]=1.[H-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:16][C@:17]([CH2:18][C:19]([CH3:21])=[CH2:20])([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[O:28][C:11]2=[O:12])[CH3:9])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 59635739HCID 59635739, compound

Product 1

HCID 46830455(R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-oneYield 34.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The crude methyl (S)-1-(4-bromophenyl)ethyl(3-hydroxy-5-methyl-3-phenylhex-5-enyl)carbamate from above procedure was dissolved in dry THF (75 mL), NaH (60% in mineral oil, 274 mg, 2 equiv) was added slowly at rt. After 10 min, the mixture was heated to reflux for 2 h. LC-MS found reaction completed. The mixture was cooled to 0° C., quenched with satd aq NH4Cl (10 mL), diluted with ether (100 mL), washed with 1% aq HCl (25 mL) and brine (15 mL), and dried over Na2SO4. After filtration and concentration, the crude product was purified by chromatography on a 40-g silica gel column, eluted with 10-35% EtOAc in hexanes. The second UV active peak was collected to afford (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-methylallyl)-6-phenyl-1,3-oxazinan-2-one (490 mg 34.5% overall yield for Steps 3 and 4).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 h
  3. customreaction
  4. customquenched with satd aq NH4Cl (10 mL)
  5. additiondiluted with ether (100 mL)
  6. washwashed with 1% aq HCl (25 mL) and brine (15 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration and concentration
  9. customthe crude product was purified by chromatography on a 40-g silica gel column
  10. washeluted with 10-35% EtOAc in hexanes
  11. customThe second UV active peak was collected

Sources & evidence

ORD record
ord-7356bbfa3476421191efe654251b5760
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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