Sodium borohydride → 1-(2,5-Difluorophenyl)propan-2-amine

Temperature

0 °C

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.

1. customIn a dry flask were placed
2. additionAfter addition
3. temperaturethe reaction mixture was heated
4. temperatureto reflux for 8 h
5. customThe reaction was quenched
6. additionby carefully pouring the mixture to water
7. temperatureheated to 80° C. for 4 h
8. customThe THF was removed under reduced pressure
9. washthe residue was washed with ether twice (2×50 mL)
10. customThe aqueous layer was separated
11. extractionextracted with ether until no product
12. waitis left in aqueous layer
13. dry with materialThe extracts were dried over anhydrous MgSO4
14. filtrationfiltered
15. customevaporated
16. custompurified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v)
17. customto give a colorless oil, 7.65 g, 88.9% yield

ORD record

ord-0bb665415cd94cdb841c433d64b3a4f2

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822500B2