Hydrogen Bromide → Ethyl 2-bromo-3-[4-methoxy-3-[N-[[4-(trifluoromethyl)phenyl]methyl]carbamoyl]phenyl]propanoate

HRID 1634520Notes

Reaction equation

HRID 1634520 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][CH2:34][CH3:35])(=[O:32])[CH:30]=[CH2:31].C(=O)([O-])O.[Na+]>[Cu]=O.O.CO.CC(C)=O>[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][CH2:34][CH3:35])=[O:32]

Participants

10

Reactant 5

HCID 260Hydrogen BromideHCID 8821Ethyl AcrylateHCID 516892Sodium BicarbonateHCID 109034245-amino-2-methoxy-N-(4-trifluoromethylbenzyl)benzamideHCID 23668193Sodium Nitrite

Product 1

HCID 10874612Ethyl 2-bromo-3-[4-methoxy-3-[N-[[4-(trifluoromethyl)phenyl]methyl]carbamoyl]phenyl]propanoateYield 71%

Reagents, catalysts & solvents 4

HCID 14829Copper oxideCatalystHCID 180AcetoneSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

5-Amino-2-methoxy-N-[[4-(trifluoromethyl)phenyl]-methyl]benzamide (7.00 g, 21.6 mmol), 85 ml of acetone and 34 ml of methanol were mixed, which was cooled with ice. Under stirring, 17.5 ml of 47% hydrobromic acid, sodium nitrite (1.65 g, 23.9 mmol) and 6.2 ml of water were added and the mixture was stirred for 10 minutes. Next, ethyl acrylate (13.4 ml, 128 mmol) and copper oxide (I) (416 mg, 2.91 mmol) were added at room temperature. After stirring for 30 minutes, the reaction mixture was poured into saturated aqueous solution of sodium hydrogencarbonate, which was extracted with ethyl acetate. The extract was washed with brine, then dried over anhydrous magnesium sulfate and concentrated. The residue was recrystallized from a mixed solvent of n-hexane with ethyl acetate to obtain 683 mg (71%) of the title compound as colorless crystals.

Workup

  1. temperaturewhich was cooled with ice
  2. stirringthe mixture was stirred for 10 minutes
  3. stirringAfter stirring for 30 minutes
  4. extractionwas extracted with ethyl acetate
  5. washThe extract was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was recrystallized from a mixed solvent of n-hexane with ethyl acetate

Sources & evidence

ORD record
ord-4d2ac8cc696048c19d61838b81f597a0
Source dataset
uspto-grants-2003_01
Patent number
US06506797B1

Reaction notes

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