Chloroacetyl chloride → (6S)-6-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholin-3-one

HRID 1091357Notes

Reaction equation

HRID 1091357 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.[OH-].[K+]>ClCCl.C(O)(C)C>[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 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 59317732(S)-1-(4-Bromophenyl)-2-(((R)-1-phenylethyl)amino)ethan-1-ol

Product 1

HCID 59317733(6S)-6-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholin-3-oneYield 90.6%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of chloroacetyl chloride (24.3 g, 215 mmol) in dichloromethane (100 ml) was dropped into the ice-cooled solution of (1S)-1-(4-bromophenyl)-2-((1R)-1-phenylethylamino)ethanol (62.6 g, 215 mmol) and triethylamine (21.8 g, 215 mmol) in dichloromethane (600 ml) over 30 minutes and the mixture was stirred for one hour at the same temperature. Resulting solution was washed with 0.5 M hydrochloric acid, saturated sodium hydrogen carbonate, brine and dried over anhydrous magnesium sulfate. The solvents were removed under reduced pressure and potassium hydroxide (85%, 16.1 g, 244 mmol) was added to a solution of resulting pale brown oil in isopropyl alcohol (600 ml) and stirred for 16 hours. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The organic layer was washed with 0.5 M hydrochloric acid, saturated sodium hydrogen carbonate, brine and dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure furnished (6S)-6-(4-bromophenyl)-4-((1R)-1-phenyethyl)morpholin-3-one (70.2 g) as a brown oil.

Workup

  1. washResulting solution was washed with 0.5 M hydrochloric acid, saturated sodium hydrogen carbonate, brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. additionwas added to a solution
  4. stirringstirred for 16 hours
  5. customThe solvent was removed in vacuo
  6. customthe residue was partitioned between water and ethyl acetate
  7. washThe organic layer was washed with 0.5 M hydrochloric acid, saturated sodium hydrogen carbonate, brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-a35d5082053a486dbdd9d4f23a12ca62
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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