Methanol → tert-butyl (2R,3S)-3-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Temperature

15 °C

The product from Example 18A (7.73 g, 33.5 mmol) in dry THF (100 mL) was treated with borane-methyl sulfide complex (10M in THF, 7.4 mL, 74 mmol) dropwise over 10 minutes. The solution was warmed to reflux for 1 hour, then cooled to 10-20° C. Methanol was added cautiously at 10-20° C. until there was no obvious evolution of hydrogen. The mixture was concentrated under reduced pressure and the white residue stirred with water (50 mL) for 10 minutes and then extracted with ethyl acetate (3×100 mL). The combined extracts were washed with brine (2×10 mL), dried (Na2SO4), and concentrated to provide the title compound as a white solid (7.24 g, 99% yield). 1H NMR (MeOH-d4, 300 MHz) δ 1.48 (s, 9H), 1.82 (m, 1H), 2.10 (m, 1H), 3.45 (m, 3H), 3.66 (m, 2H), 4.30 (m, 1H); MS (DCI/NH3) m/z 218 (M+H)+.

1. temperatureThe solution was warmed
2. temperatureto reflux for 1 hour
3. concentrationThe mixture was concentrated under reduced pressure
4. extractionextracted with ethyl acetate (3×100 mL)
5. washThe combined extracts were washed with brine (2×10 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated

ORD record

ord-28622d15cad641d6985f9bd4435f2055

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119635B2