Tetrahydrofuran → HCID 66703639, compound

Temperature

0 °C

To a stirred solution of (R)-1-(2,5-difluorophenylmethyl)-3-chloro-2-oxopropylcarbamic acid tert-butyl ester (3.56 g, 11 mmol) in a solution of 9:1 THF:water (150 mL) at 0° C. is added NaBH4 (0.49 g, 13 mmol, 1.2 eq) and stirred for 5 min. The reaction mixture is concentrated under reduced pressure to a white solid which is suspended in a mixture of water and ethyl acetate. This biphasic mixture is cooled to 0° C. and quenched slowly with 2M NaHSO4 until pH˜2 and the layers rapidly separated. The organic layer is washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford a white solid as a mixture of diastereomers (3.5 g, 13 mmol, ˜5:2 R,R:R,S). The crude material was purified using General Purification Procedure C to afford the title compound as a single diastereomer of a white solid (2.2 g, 6.6 mmol).

1. concentrationThe reaction mixture is concentrated under reduced pressure to a white solid which
2. additionis suspended in a mixture of water and ethyl acetate
3. customquenched slowly with 2M NaHSO4 until pH˜2
4. customthe layers rapidly separated
5. washThe organic layer is washed with water and brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customto afford a white solid
9. additionas a mixture of diastereomers (3.5 g, 13 mmol, ˜5:2 R,R:R,S)
10. customThe crude material was purified
11. customGeneral Purification Procedure C

ORD record

ord-a3b330f3e9ea4ad7b6eff2fbb97b6aab

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08106090B2