Methanol → 4-{(S)-1-[(S)-6-(2-Hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-benzoic acid methyl ester

HRID 80962Notes

Reaction equation

HRID 80962 reaction equation
CCN(CC)CC.Br[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@:20]([CH2:29][C:30]([OH:33])([CH3:32])[CH3:31])([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[O:19][C:18]2=[O:34])[CH3:16])=[CH:11][CH:10]=1.CN(C)[CH:37]=[O:38].[CH3:40][OH:41]>CC#N>[CH3:40][O:41][C:37](=[O:38])[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@:20]([CH2:29][C:30]([OH:33])([CH3:31])[CH3:32])([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[O:19][C:18]2=[O:34])[CH3:16])=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 44599033(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

Product 1

HCID 581095974-{(S)-1-[(S)-6-(2-Hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

NEt3 (0.47 mL) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II)dichloromethane complex (0.15 g) were added to a solution of 3-[(S)-1-(4-bromo-phenyl)-ethyl]-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one (1.04 g) in MeCN (2.5 mL), methanol (20 mL), and N,N-dimethylformamide (5 mL). The resulting mixture was sparged with argon for 5 min and then transferred to a pressure-resistant vessel that was filled with CO (5.5. bar). The mixture was heated to 70° C. and stirred at this temperature for 18 h before another portion of [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II)dichloromethane complex (0.15 g) was added. After stirring at 70° C. for another 4 h, the mixture was cooled to ambient temperature, filtered, and concentrated under reduced pressure. The residue was taken up in ethyl acetate and the resulting mixture was washed with water and brine and dried (MgSO4). The solvent was removed and the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 40:60→0:100) to afford the title compound as an oil.

Workup

  1. customThe resulting mixture was sparged with argon for 5 min
  2. customtransferred to a pressure-resistant vessel
  3. additionthat was filled with CO (5.5. bar)
  4. additionwas added
  5. stirringAfter stirring at 70° C. for another 4 h
  6. temperaturethe mixture was cooled to ambient temperature
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. washthe resulting mixture was washed with water and brine
  10. dry with materialdried (MgSO4)
  11. customThe solvent was removed
  12. customthe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 40:60→0:100)

Sources & evidence

ORD record
ord-c0ed32d67aaa4b35b9349fae62f52a40
Source dataset
uspto-grants-2014_09
Patent number
US08846668B2

Reaction notes

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