Sodium borohydride → tert-butyl (2S,3S)-4-chloro-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate

To a solution of the crude (S)-tert-butyl 4-chloro-1-cyclohexyl-3-oxobutan-2-ylcarbamate (5.8 g, 0.019 mol) in 9:1 THF/H2O (100 mL) at 0° C. was added NaBH4 (1.8 g, 0.047 mmol). After stirring for 45 min at rt, the solvent was removed in vacuo. The residue was diluted with water (50 mL) and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product which was purified by flash chromatography to give a mixture of isomeric alcohols, which was recrystallized from n-hexane three times to give pure tert-butyl (2S,3S)-4-chloro-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate (1.15 g, 40%). 1H NMR: 0.82 (m, 1H), 0.96 (m, 1H), 1.08-1.40 (m, 5H), 1.43 (s, 9H), 1.65 (m, 4H), 1.82 (m, 1H), 3.08 (m, 1H), 3.52 (m, 1H), 3.58 (r, 1H), 3.79 (m, 2H), 4.51 (m, 1H). MS (E/Z): 306 (M+H+). The mother liquor was concentrated and recrystallized from n-hexane three times to give pure tert-butyl (2S,3R)-4-chloro-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate (0.3 g, 10.3%).

1. customthe solvent was removed in vacuo
2. additionThe residue was diluted with water (50 mL)
3. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give the crude product which
9. customwas purified by flash chromatography
10. customto give
11. customwas recrystallized from n-hexane three times

ORD-Eintrag

ord-641709d3a61346fb9fcac7b7977d2b1e

Quelldatensatz

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07872028B2