Sodium borohydride → 1-(2,5-Difluorophenyl)propan-2-amine
反応式
[BH4-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[CH:11]=[C:12]([N+:14]([O-])=O)[CH3:13]>C1COCC1>[F:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[CH2:11][CH:12]([NH2:14])[CH3:13]参加物
4
反応条件
- 温度
- 0 °C
実験手順
In a dry flask were placed NaBH4 (9.50 g, 0.251 mol) and 300 mL of dry THF. The flask was cooled to 0° C. under argon and 42.76 g of BF3(Et2O) was added via a syringe. After addition, a solution of 10.0 g (50.21 mmol) of 1-(2,5-difluorophenyl)-2-nitropropene was added dropwise via a syringe, and the reaction mixture was heated to reflux for 8 h. The reaction was quenched by carefully pouring the mixture to water, acidified with 2 N HCl and heated to 80° C. for 4 h. The THF was removed under reduced pressure; the residue was washed with ether twice (2×50 mL). The aqueous layer was separated, made strongly alkaline with 10% aqueous NaOH solution and extracted with ether until no product is left in aqueous layer. The extracts were dried over anhydrous MgSO4, filtered, evaporated and purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give a colorless oil, 7.65 g, 88.9% yield. MS: 172.0 [M+H]+. 1H NMR (DMSO-d6, 500 MHz): δ 7.20-7.13 (m, 1H), 7.10-7.05 (m, 2H), 3.06 (sextet, 1H, J=6.5 Hz), 2.63-2.54 (m, 2H), 0.96 (d, 3H, J=6.0 Hz). Racemate status was confirmed by HPLC using a chiral column as described for compound D below.