反应详情

To a stirred suspension of N-methylformanilide (67.6 g; 0.50 mole), toluene (25 g) and 2-aminothiazole (2.0 g; 0.02 mole) was added phosphorus oxychloride (45.8 mL; 0.50 mole) over 15 minutes. The temperature was maintained below 45° C. during this addition. Stirring was continued for 10 minutes, after which time a hot solution of 2-aminothiazole (48.0 g; 0.48 mole) in toluene (250 g) was added at 60°-65° C. over 45 minutes. The reaction was allowed to cool to room temperature with stirring and was quenched by dropwise addition into a mixture of 30% sodium hydroxide (325 g) and ice (300 g). The organic phase was washed with a mixture of water (100 g), sodium chloride (10 g), and sodium bicarbonate (7.5 g), followed by a saturated solution of sodium chloride (125 g); the resultant organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated to yield 98.3 g of crude product. Vacuum distillation gave pure 1 (60.0 g; 55.3%) as a yellow oil: bp 177° C. @ 0.5 mm Hg. 1H-NMR (CDCl3) 8.72 (s, 1H), 7.4-6.9 (m, 7H), 3.50 (S, 3H); IR(neat) 3075, 2950, 1615, 1580, 1490, 1345, 1310, 1120; MS (m/e) 217 (M+, base).

1. temperatureThe temperature was maintained below 45° C. during this addition
2. stirringwith stirring
3. customwas quenched by dropwise addition into a mixture of 30% sodium hydroxide (325 g) and ice (300 g)
4. washThe organic phase was washed with a mixture of water (100 g), sodium chloride (10 g), and sodium bicarbonate (7.5 g)
5. dry with materialthe resultant organic layer was dried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated