反应详情

温度

40 °C

A 22 L, 3 neck flask, equipped with an overhead stirrer, electric heating mantle, condenser, an N2 inlet, and a type-J Teflon® covered thermocouple, was charged with nitrile 10 (797 g, 2.49 moles—corrected for a purity of 75% by weight), formic acid (6400 ml) and magnesium sulfate (510 g). The resulting brown viscous mixture was heated to 40° C. with stirring and was allowed to stir at that temperature for 4 hours. At that time the reaction was judged to be complete by TLC and LC analysis. The reaction mixture was allowed to cool to 20° C. and stir at that temperature overnight. The following morning the reaction mixture was poured into 24 liters of water. The resulting yellow solid was collected by vacuum filtration rinsing with water (2×1500 ml) followed by isopropanol displacement wash (1×1500 ml). The crude product was allowed to air dry to a constant weight to afford 1030 g (886 g corrected for purity of 86% by weight-103%). The water content was 1.02% by Karl Fischer titration. The material was used directly in the next step without further purification. Rf=0.37 (65% EtOAc/hexanes) HPLC 10:90 to 90:10 CH3CN:H2O over 15 min. Hold at 90:10 for 2 min, 0.025% TFA Buffer, 1.5 mL/min, UV at 220 nm, Phenomenex Jupiter C18 column 4.6 mm×250 mm at 29° C.: (st. material 11.6 min, amide 9.26 min, 87 A %) 1H NMR (DMSO, 300 MHz): 2.61-2.65 (m, 2H), 3.09-3.13 (m, 2H), 4.13 (s, 2H), 4.64 (s, 2H), 7.29-7.49 (m, 5H), 7.84 (br, 1H), 8.12 (s, 1H), 8.49 (br, 1H), 8.74 (s, 1H), 12.57 (br, 1H).

1. customA 22 L, 3 neck flask, equipped with an overhead stirrer
2. stirringto stir at that temperature for 4 hours
3. temperatureto cool to 20° C.
4. stirringstir at that temperature overnight
5. filtrationThe resulting yellow solid was collected by vacuum filtration
6. washrinsing with water (2×1500 ml)
7. washwash (1×1500 ml)
8. customto air dry to a constant weight
9. customto afford 1030 g (886 g corrected for purity of 86% by weight-103%)
10. customThe material was used directly in the next step without further purification
11. waitHold at 90:10 for 2 min
12. customat 29° C.
13. custommaterial 11.6 min, amide 9.26 min, 87