Hydrochloric Acid → (2S,3R)-methyl-3-(difluoromethoxy)-2-(methoxycarbonylamino)butanoate

Temperature

50 °C

To a solution of 2-tert-Butoxycarbonylamino-3-difluoromethoxy-butyric acid methyl ester (3 g, 10.6 mmol) in methanol (40 mL) was added concentrated HCl solution (10 mL) and the reaction was stirred at 50° C. for 1 hour. The reaction was concentrated on a rotary evaporator and the resulting residue was basified with saturated NaHCO3 solution. The aqueous layer was extracted twice with ethyl acetate. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated. To a solution of the crude material in dichloromethane (50 mL) was added diisopropylethylamine (4.2 mL, 24.2 mmol), followed by methyl chloroformate (0.95 mL, 12.3 mmol). The reaction was stirred at room temperature for 2 hours, quenched by the careful addition of saturated NH4Cl solution and diluted with ethyl acetate. The organic layer was separated, washed with water and brine, dried (MgSO4) and concentrated. The crude material was purified by flash chromatography to yield (2S,3R)-methyl-3-(difluoromethoxy)-2-(methoxycarbonylamino)butanoate (1.2 g, 47%).

1. concentrationThe reaction was concentrated on a rotary evaporator
2. extractionThe aqueous layer was extracted twice with ethyl acetate
3. customThe organic layer was separated
4. washwashed with brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. stirringThe reaction was stirred at room temperature for 2 hours
8. customquenched by the careful addition of saturated NH4Cl solution
9. additiondiluted with ethyl acetate
10. customThe organic layer was separated
11. washwashed with water and brine
12. dry with materialdried (MgSO4)
13. concentrationconcentrated
14. customThe crude material was purified by flash chromatography

ORD record

ord-3f07bfd3e87a4db9af0881f08b2f5654

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156823B2