Dimethylformamide → 6-chloro-5-fluoro-1H-indole-3-carbaldehyde
Reaction equation
O=P(Cl)(Cl)Cl.[Cl:6][C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[CH:12][NH:13]2)=[CH:9][C:8]=1[F:16].CN(C)[CH:19]=[O:20]>>[Cl:6][C:7]1[CH:15]=[C:14]2[C:10]([C:11]([CH:19]=[O:20])=[CH:12][NH:13]2)=[CH:9][C:8]=1[F:16]Participants
4
Conditions
- Temperature
- 35 °C
Procedure
POCl3 (2.43 mL, 26.53 mmol) was added dropwise to N,N-dimethylformamide (15.0 mL) at −20° C. and stirred below −5° C. for one hour. A solution of 6-chloro-5-fluoroindole (3.0 g, 17.69 mmol) in dimethylformamide (5.0 mL) was added dropwise to the above reaction mixture at −20° C. The salt-ice bath was removed and the reaction mixture was warmed to 35° C. After one hour, the reaction was poured onto ice and basified by solid sodium bicarbonate and extracted with ethyl acetate. The combined organic layer was washed with water and then concentrated to give 6-chloro-5-fluoro-1H-indole-3-carbaldehyde (3.4 g, 97%) as a light brown solid. 1H NMR (500 MHz, CDCl3): δ 10.02 (s, 1 H), 8.10 (d, 1H, J=9.5 Hz), 7.87 (s, 1 H), 7.49 (d, 1H, J=5.5 Hz).