Sodium borohydride → (R,R)-1-benzyl-3-chloro-2-hydroxypropylcarbamic acid tert-butyl ester

Temperature

0 °C

To a stirred solution of (R)-1-Benzyl-3-chloro-2-oxopropylcarbamic acid tert-butyl ester (8.0 g, 27 mmol) in THF/water (200 mL, 9/1, v/v) at 0° C. is added NaBH4 (1.23 g, 32 mmol). After 30 min the mixture is concentrated under reduced pressure and the residue is suspended in a mixture of water and ethyl acetate (1:1, v/v). This mixture is cooled to 0° C. and the pH is adjusted to ˜2 by the slow addition of 2M NaHSO4. The phases are separated and 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 (7.92 g, 27 mmol, ˜5:2 R,R:R,S), which is purified using General Purification Procedure C to afford the title compound as a white solid (4.45 g, 15 mmol).

1. concentrationAfter 30 min the mixture is concentrated under reduced pressure
2. additionthe residue is suspended in a mixture of water and ethyl acetate (1:1
3. additionthe pH is adjusted to ˜2 by the slow addition of 2M NaHSO4
4. customThe phases are 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 (7.92 g, 27 mmol, ˜5:2 R,R:R,S), which
10. customis purified
11. customGeneral Purification Procedure C

ORD record

ord-825d786553ee4a8e927edb40b11b1aab

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08106090B2