4-Methylmorpholine → tert-butyl ((2R,3R)-1-hydroxy-3-methoxybutan-2-yl)carbamate

Temperature

-30 °C

To a round bottom flask containing a stir bar and (2S,3R)-2-((tert-butoxycarbonyl)amino)-3-methoxybutanoic acid (2.5 g, 10.7 mmol) in THF (80 mL) under nitrogen was cooled to −30° C. in a dry ice/acetone bath. To this cold solution was added isobutyl chloroformate (1.7 mL, 12.9 mmol) followed by the addition of N-methylmorpholine (1.4 mL, 12.9 mmol). Mixture was stirred for 15 min at −30° C. N-Methylmorpholine salt develops and was filtered from mixture. Mother liquor was cooled to −30° C. where upon sodium borohydride (0.61 g, 16.1 mmol) was added followed by the addition of water (10 mL) immediately afterwards. Reaction mixture allowed to stir for 15 min at −20° C. then gradually allowed to warm to room temperature. Reaction mixture was stirred for 30 min at room temperature. Reaction mixture was then diluted with water and extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated to afford tert-butyl((2R,3R)-1-hydroxy-3-methoxybutan-2-yl)carbamate (2.0 g, 9.1 mmol, 85% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.18 (d, J=6.26 Hz, 3H) 1.45 (s, 9H) 3.33 (s, 3H) 3.55-3.84 (m, 4H). LCMS m/z 220.2 (M+H)+, Rt 0.57 min.

1. additionTo a round bottom flask containing a stir bar
2. filtrationwas filtered from mixture
3. additionwas added
4. customReaction mixture
5. stirringto stir for 15 min at −20° C.
6. temperatureto warm to room temperature
7. customReaction mixture
8. stirringwas stirred for 30 min at room temperature
9. customReaction mixture
10. extractionextracted with EtOAc
11. washwashed with water, brine
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-fa303966dbb84f32a4eb38cf328732a2

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434719B2