反应详情

温度

47 °C

An aqueous solution of methylamine (40 wt %, 910 ml) at 30° C. is added to a 61° C. solution of 4-(3-fluoro-4-nitrobenzyl)morpholine (504 g) in DMSO (810 ml) followed by a DMSO rinse (150 ml) over ½ h. The mixture is allowed to reflux at 47 ° C. over 5 min then maintained at <51° C. by occasional ice bath cooling for remainder of the addition. The mixture is stirred at 50° C. for ¾ h and then water (2000 ml) is added. The mixture is cooled to 0° C. and the precipitate is collected by filtration, washed with water (1500 ml) and is dried in a nitrogen stream to give a bright orange solid (529 g). Physical characteristics: 1H NMR (400 MHz, DMSO-d6) δ2.35, 2.93, 3.44, 3.56, 6.63, 6.64, 7.78, 8.15; 13C NMR (100 MHz, DMSO-d6) δ29.95, 53.57, 62.27,66.54, 113.69, 115.76, 126.49, 130.16, 146.27, 148.07.

1. washrinse (150 ml) over ½ h
2. temperaturethen maintained at <51° C. by occasional ice bath
3. temperaturecooling for remainder of the addition
4. additionwater (2000 ml) is added
5. temperatureThe mixture is cooled to 0° C.
6. filtrationthe precipitate is collected by filtration
7. washwashed with water (1500 ml)
8. customis dried in a nitrogen stream