4-Methylmorpholine → benzyl ((2R,3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate

Temperature

-20 °C

A solution of (2S,3R)-2-(((benzyloxy)carbonyl)amino)-3-(tert-butoxy)butanoic acid dicyclohexylammonium salt (500 mg, 1.0 mmol) in 10 ml of THF and isobutyl chloroformate (167 mg, 1.2 mmol, 1.2 equiv) at −25° C. was added N-methylmorpholine (124 mg, 1.2 mmol, 1.2 equiv), the mixture was stirred at same temperature for 10 min and filtered. The filtrate was cooled to −20° C. and to it was added NaBH4, followed by 2 ml of water immediately afterwards. The reaction mixture was stirred at same temperature for 5 min. then gradually warmed to room temperature for 25 min, poured into water (10 ml) and extracted with ethyl acetate (2×20 ml). The combined organic phases were washed with water, brine and dried over Na2SO4. The solvent was removed to yield benzyl((2R)-(3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate as a clear oil. No further purification was required for next step. 1H NMR (400 MHz, CDCl3) δ 7.37-7.16 (m, 5H), 5.25 (d, J=8.0 Hz, 1H), 5.02 (s, 1H), 4.04 (ddd, J=12.0, 8.9, 2.8 Hz, 1H), 3.92-3.75 (m, 1H), 3.59 (dddd, J=32.3, 14.6, 8.2, 4.3 Hz, 2H), 1.10 (s, 9H), 1.09-1.06 (m, 3H).

1. filtrationfiltered
2. additionwas added NaBH4
3. stirringThe reaction mixture was stirred at same temperature for 5 min.
4. temperaturethen gradually warmed to room temperature for 25 min
5. additionpoured into water (10 ml)
6. extractionextracted with ethyl acetate (2×20 ml)
7. washThe combined organic phases were washed with water, brine
8. dry with materialdried over Na2SO4
9. customThe solvent was removed

ORD record

ord-27593acdd5a64e5bab6ece9613d5e0da

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434719B2