Hydrogen Bromide → methyl 2-bromo-3-[4-methoxy-3-[N-(4-trifluoromethylbenzyl)]carbamoylphenyl]-propionate

HRID 49534

Reaction equation

HRID 49534 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]([CH:21]=1)[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1)=[O:8].[BrH:24].N([O-])=O.[Na+].[C:29]([O:33][CH3:34])(=[O:32])[CH:30]=[CH2:31]>CC(C)=O.CO>[Br:24][CH:30]([CH2:31][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]([C:7](=[O:8])[NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[CH:21]=1)[C:29]([O:33][CH3:34])=[O:32]

Participants

7

Reactant 4

HCID 260Hydrogen BromideHCID 7294Methyl AcrylateHCID 109034245-amino-2-methoxy-N-(4-trifluoromethylbenzyl)benzamideHCID 23668193Sodium Nitrite

Product 1

HCID 12094665methyl 2-bromo-3-[4-methoxy-3-[N-(4-trifluoromethylbenzyl)]carbamoylphenyl]-propionate

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of 17.3 g of 5-amino-2-methoxy-N-(4-trifluoromethylbenzyl)benzamide in 170 ml of acetone and 85 ml of methanol were added 43 ml of 47% solution of hydrobromic acid and 17 ml of aqueous solution of 4.15 g of sodium nitrite under cooling with ice-salt, and the mixture was stirred for 10 minutes. To the reaction mixture were added 26 ml of methyl acrylate, and, after heated to 30° C., 1.04 g of cupric oxide were added little by little, and the mixture was stirred further for 1 hour at 40 to 50° C. Solvent was distilled off under reduced pressure, and 25% aqueous ammonia was added to the residue, which was extracted with ethyl acetate. The organic layer was washed with water and saturated brine in sequence and dried over anhydrous sodium sulfate. Solvent was distilled off under reduced pressure, and the residue obtained was crystallized from hexane-ethyl acetate, then the crystals were collected by filtration to obtain 10.3 g of methyl 2-bromo-3-[4-methoxy-3-[N-(4-trifluoromethylbenzyl)]carbamoylphenyl]-propionate as light brown crystals.

Workup

  1. stirringwas stirred further for 1 hour at 40 to 50° C
  2. distillationSolvent was distilled off under reduced pressure, and 25% aqueous ammonia
  3. additionwas added to the residue, which
  4. extractionwas extracted with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine in sequence
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationSolvent was distilled off under reduced pressure
  8. customthe residue obtained
  9. customwas crystallized from hexane-ethyl acetate
  10. filtrationthe crystals were collected by filtration

Sources & evidence

ORD record
ord-faaa6191dbe04481811664c513cd2e9a
Source dataset
uspto-grants-2004_03
Patent number
US06706763B1

Linked notes

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