Chloroacetyl chloride → 4-Benzyl-6-(4-bromo-phenyl)-morpholin-3-one

HRID 2063359Notes

Reaction equation

HRID 2063359 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[CH2:6]([NH:13][CH2:14][CH:15]([C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=1)[OH:16])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.C[O-].[Na+]>C1(C)C=CC=CC=1.CO>[CH2:6]([N:13]1[CH2:14][CH:15]([C:17]2[CH:18]=[CH:19][C:20]([Br:23])=[CH:21][CH:22]=2)[O:16][CH2:2][C:3]1=[O:4])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 10942334Sodium MethoxideHCID 580978892-Benzylamino-1-(4-bromo-phenyl)-ethanol2×

Product 1

HCID 580978854-Benzyl-6-(4-bromo-phenyl)-morpholin-3-oneYield 86%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent3×

Procedure

After addition of chloroacetyl chloride (8.49 g, 75.2 mmol) in toluene (30 ml) to a ice-cooled solution of 2-benzylamino-1-(4-bromo-phenyl)-ethanol (intermediate 31, 21.85 g, 71.4 mmol) in toluene (300 ml), a solution of triethylamine (10.25 g, 101 mmol) in toluene (20 ml) was added to the mixture and stirred for one hour. Sodium methoxide (28% solution in methanol, 45.73 g, 237 mmol) in methanol (30 ml) was then added to the solution and stirred for 2 hours. Reaction was quenched by adding dilute hydrochloric acid to adjust the pH around 7.0, and partitioned between water and ethyl acetate. The organic layer was washed with dilute hydrochloric acid, water, saturated aqueous sodium bicarbonate, and brine and dried over sodium sulfate. Solvents were removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=1/1) to afford 4-benzyl-6-(4-bromo-phenyl)-morpholin-3-one (intermediate 32, 21.26 g, 86%) as a colorless oil.

Workup

  1. stirringstirred for 2 hours
  2. customReaction
  3. customwas quenched
  4. additionby adding dilute hydrochloric acid
  5. custompartitioned between water and ethyl acetate
  6. washThe organic layer was washed with dilute hydrochloric acid, water, saturated aqueous sodium bicarbonate, and brine
  7. dry with materialdried over sodium sulfate
  8. customSolvents were removed under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-4c9e41abf45843889c25a2df2227748e
Source dataset
uspto-grants-2012_10
Patent number
US08288383B2

Reaction notes

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