反应详情

温度

50 °C

A 5 L three-necked round-bottomed flask, equipped with a mechanical stirrer, a condenser and a thermometer, was charged with 2,5-difluorobenzaldehyde (142.11 g, 1 mole). Toluene (500 ml), acetonitrile (500 ml), formamide (99.3 ml, 2.5 moles) and chlorotrimethylsilane (139.6 ml, 1.1 moles) were added respectively. The cloudy mixture was heated to 50° C. and stirred at this temperature for 7 hours. p-Toluenesulfinic acid (218.68 g, 1.4 moles) was added. The mixture was stirred at 50° C. for 6 hours and then 13 hours at room temperature. Methyl t-butyl ether (1.8 L) and water (1.7 L) were then added. The mixture was stirred at room temperature for 15 minutes at which time the organic layer was separated. The aqueous layer was extracted with methyl t-butyl ether (500 ml). Most of the solvents were removed from the combined organic extracts. To the residual white semi-solid, hexane (1 L) and water (1 L) were added. The slurry was stirred at room temperature for 30 minutes and filtered. The cake was washed with hexane (2×200 ml) and dried in a vacuum-oven (30° C.) for 18 hours. The product, N-[(2,5-Difluoro-phenyl)-(toluene-4-sulfonyl)-methyl]-formamide (258.3 g, yield 79%,), was obtained as a white powder.

1. customA 5 L three-necked round-bottomed flask, equipped with a mechanical stirrer, a condenser
2. stirringThe mixture was stirred at 50° C. for 6 hours
3. custom13 hours
4. customat room temperature
5. stirringThe mixture was stirred at room temperature for 15 minutes at which time the organic layer
6. customwas separated
7. extractionThe aqueous layer was extracted with methyl t-butyl ether (500 ml)
8. customMost of the solvents were removed from the combined organic extracts
9. additionTo the residual white semi-solid, hexane (1 L) and water (1 L) were added
10. stirringThe slurry was stirred at room temperature for 30 minutes
11. filtrationfiltered
12. washThe cake was washed with hexane (2×200 ml)
13. customdried in a vacuum-oven (30° C.) for 18 hours