Tetrahydrofuran → benzyl N-[(3R,4S)-4-hydroxyoxolan-3-yl]carbamate

Temperature

0 °C

A mixture of the crude trans-4-aminotetrahydrofuran-3-ol (from Step 1), sodium carbonate (7.68 g, 72.5 mmol), tetrahydrofuran (100 mL) and water (100 mL) was cooled to 0° C. and stirred vigorously. Benzyl chloroformate (9.48 mL, 66.4 mmol) was added dropwise. The resulting mixture was stirred at room temperature for 2 h. The organic solvent was removed in vacuo. The aqueous residue was diluted with water (50 mL) and extracted with ethyl acetate (3×70 mL). The combined extracts were dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 30-100% ethyl acetate in hexanes, gave benzyl trans-4-hydroxytetrahydrofuran-3-ylcarbamate as a white solid (8.43 g, 59% yield for 2 steps). 1H NMR (400 MHz, chloroform-d) δ ppm 7.28-7.51 (5 H, m), 5.11 (2 H, br. s.), 4.92 (1 H, br. s.), 4.32 (1 H, br. s.), 3.93-4.17 (3 H, m), 3.50-3.80 (2 H, m), 2.69 (1 H, br. s.); MS (ES+) m/z: 238.1 (M+H); LC retention time: 2.595 min (analytical HPLC Method H).

1. stirringThe resulting mixture was stirred at room temperature for 2 h
2. customThe organic solvent was removed in vacuo
3. additionThe aqueous residue was diluted with water (50 mL)
4. extractionextracted with ethyl acetate (3×70 mL)
5. dry with materialThe combined extracts were dried (MgSO4)
6. concentrationconcentrated
7. washSilica gel chromatography, eluting with 30-100% ethyl acetate in hexanes

ORD record

ord-d2d99363345a4e978bbfade5eb8f614d

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987268B2