Hydrochloric Acid → (6S)-6-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholin-3-one

HRID 218316Notes

Reaction equation

HRID 218316 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[Br:6][C:7]1[CH:12]=[CH:11][C:10]([C@H:13]([OH:24])[CH2:14][NH:15][C@@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH3:17])=[CH:9][CH:8]=1.C(N(CC)CC)C.Cl.[OH-].[K+]>ClCCl>[Br:6][C:7]1[CH:8]=[CH:9][C:10]([C@H:13]2[CH2:14][N:15]([C@@H:16]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH3:17])[C:3](=[O:4])[CH2:2][O:24]2)=[CH:11][CH:12]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 59317732(S)-1-(4-Bromophenyl)-2-(((R)-1-phenylethyl)amino)ethan-1-ol2×

Product 1

HCID 59317733(6S)-6-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholin-3-oneYield 115%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of chloroacetyl chloride (19.5 ml, 245 mmol) in dichloromethane (100 ml) was added dropwise to a ice-cooled solution of (1S)-1-(4-bromophenyl)-2-((1R)-1-phenylethylamino)ethanol (intermediate 11, 71.0 g, 222 mmol) and triethylamine (34 ml, 245 mmol) in dichloromethane (600 ml). After the mixture was stirred for 2 hours, 1 M hydrochloric acid was added and the mixture was partitioned between water and chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was dissolved in 2-propanol (600 ml). The solution was added with potassium hydroxide (85%, 18.3 g, 278 mmol). The mixture was stirred at room temperature for 15 hours. The solvent was evaporated under reduced pressure and the residue was added with ethyl acetate. The mixture was partitioned between water and ethyl acetate, and the organic layer was washed with 1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give (6S)-6-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholin-3-one (intermediate 12, 92 g) as a brown oil. This crude product was used for next reaction without purification.

Workup

  1. customthe mixture was partitioned between water and chloroform
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in 2-propanol (600 ml)
  6. stirringThe mixture was stirred at room temperature for 15 hours
  7. customThe solvent was evaporated under reduced pressure
  8. additionthe residue was added with ethyl acetate
  9. customThe mixture was partitioned between water and ethyl acetate
  10. washthe organic layer was washed with 1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-efcdcfff9cda43ba9662411f34583118
Source dataset
uspto-grants-2012_06
Patent number
US08198437B2

Reaction notes

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