Trifluoroacetic acid → Isoxazolidine-2-sulfonamide

To a cold (0° C.) solution of chlorosulfonyl isocyanate (0.437 mL, 5.02 mmol) in CH2Cl2 (10 mL) was added tert-BuOH (0.480 mL, 5.02 mmol) and the mixture was stirred for 1 h at 0° C. Then HCl salt of isoxazolidine (0.5 g, 4.56 mmol) and TEA (1.399 mL, 10.04 mmol) were added consecutively and the mixture was stirred overnight. Rxn was diluted with EtOAc and washed with ice cold 1N HCl, brine and then dried (MgSO4). Isolated crude product was purified by Biotage 25M column to afford tert-butyl isoxazolidin-2-ylsulfonylcarbamate as a beige solid (0.82 g, 71%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.50 (9 H, s), 2.38 (2 H, quin, J=7.37 Hz), 3.81 (2 H, m), 4.19 (2 H, t, J=7.30 Hz). To a cold (0-5° C.) solution of tert-butyl isoxazolidin-2-ylsulfonylcarbamate (0.82 g, 3.25 mmol) in DCM (2 mL) was added TFA (2 mL, 35.1 mmol) and the reaction mixture was stirred for 2 h at r.t and removed the solvent to afford isoxazolidine-2-sulfonamide (0.229 g, 46%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 2.40 (2 H, quin, J=7.32 Hz), 3.65 (2 H, m), 4.20 (2 H, t, J=7.32 Hz), 4.83 (2 H, brs).

1. customremoved the solvent

ORD record

ord-6e6b8486f09b489984bbce7c956ebff1

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538102B2