Hydrochloric Acid → N-(3,5-difluorophenyl)-3,3-bis(methyloxy)propanamide
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:9])[CH:8]=1)[NH2:5].[CH3:10][O:11][C:12](=[O:17])[CH:13]=[CH:14][O:15]C.[CH3:18][O-].[Na+].[Cl-].[NH4+].Cl>C1(C)C=CC=CC=1.CO>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:14](=[O:15])[CH2:13][CH:12]([O:17][CH3:18])[O:11][CH3:10])[CH:6]=[C:7]([F:9])[CH:8]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 70 °C
Procedure
A solution of 3,5-difluoroaniline (5 g, 38.8 mmol), methyl-3-methoxyacrylate (4.6 ml, 42.7 mmol) and sodium methoxide solution (25% in MeOH, 12 ml) in toluene (50 ml) under Argon was stirred at 70° C. for 3 h. More sodium methoxide solution (25% in MeOH, 6 mL) added and reaction stirred overnight. Still more sodium methoxide solution (25% in MeOH, 12 mL) and methyl-3-methoxyacrylate (5 mL, 46.4 mmol) were then added and reaction was heated at 70° C. for 5 h. MeOH was added and volume of toluene was reduced to about 10 ml. The residue was acidified to pH 7 using a saturated solution of ammonium chloride, solid ammonium chloride and 5N HCl. The aqueous phase was extracted using ethyl acetate (2×500 ml). The combined organic phases were dried, evaporated and the residue was chromatographed on silica gel, eluting with 0-100% ethyl acetate-40-60° C. petroleum ether to afford the impure desired compound (12 g, 126%).
Workup
- customreaction
- customreaction
- extractionThe aqueous phase was extracted
- customThe combined organic phases were dried
- customevaporated
- customthe residue was chromatographed on silica gel
- washeluting with 0-100% ethyl acetate-40-60° C. petroleum ether
Sources & evidence
- ORD record
- ord-896f8d997f37489995025d3895b6ec80
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08071592B2
Reaction notes
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