Reaction equation
[CH2:1]([O:3][C:4](=[O:12])[CH:5]=[C:6]([NH2:11])[C:7]([F:10])([F:9])[F:8])[CH3:2].[C:13](Cl)(=[O:16])[CH:14]=[CH2:15].Cl>C1(C)C=CC=CC=1.CCCCCCC>[CH2:1]([O:3][C:4]([C:5]1[CH2:15][CH2:14][C:13](=[O:16])[NH:11][C:6]=1[C:7]([F:10])([F:8])[F:9])=[O:12])[CH3:2]Participants
Procedure
To 3-amino-4,4,4-trifluoro-2-butenoic acid ethyl ester (529 mL, 3.47 mol) was added acryloylchloride (600 mL, 6.95 mol) dropwise over a period of 15 min. The suspension was stirred at RT for 1 h. The temperature was slowly raised with stirring to 80° C. (HCl gas evolution) and maintained at 80° C. for 5 h. Stirring continued overnight at 40° C. The mixture was cooled, diluted with toluene (2 L) and n-heptane (2 L) to precipitate the product and stirred for another 15 min at room temperature. The product was isoloated by filtration, the filter cake was washed with toluene/n-heptane (1:2; 4×100 mL) and dried in vacuo at 40° C. for 5 h. This procedure yielded the title compound (286 g, 35%) as a white solid, MS (ISP) 236.1 (M−H)−. Concentration of the mother liquor and addition of toluene/n-heptane (1:10) yielded a second crop of 29.8 g.
Workup
- temperatureThe temperature was slowly raised
- temperaturemaintained at 80° C. for 5 h
- stirringStirring
- waitcontinued overnight at 40° C
- temperatureThe mixture was cooled
- customto precipitate the product
- stirringstirred for another 15 min at room temperature
- filtrationThe product was isoloated by filtration
- washthe filter cake was washed with toluene/n-heptane (1:2; 4×100 mL)
- customdried in vacuo at 40° C. for 5 h
Sources & evidence
- ORD record
- ord-54a8f275ab634a6e8849c5ba7621e217
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07897621B2
Linked notes
Loading…