Water → tert-butyl (2S,4R)-4-hydroxy-2-(2-methoxy-2-oxoethyl)pyrrolidine-1-carboxylate

The solution of tert-butyl (2R,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(cyanomethyl)pyrrolidine-1-carboxylate (7.81 g, 22.9 mmol, step 1 of Example 9) in concentrated hydrochloric acid-acetic acid (50 mL-50 mL) was refluxed for 15 h and concentrated under reduced pressure. The resulting residue was dissolved in 10% hydrochloric acid in methanol (50 mL). The mixture was refluxed for 18 h and concentrated under reduced pressure. To the suspension of resulting residue in dichloromethane (100 mL) were added triethylamine (9.58 mL, 68.7 mmol) and di-tert-butyl dicarbonate (7.50 g, 34.4 mmol) at 0° C. The mixture was allowed to warm to room temperature and stirred for 14 h. To the mixture was added water (100 mL). The organic layer was separated, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (1:1) to give 4.23 g (71%) of the title compound as a colorless oil.

1. concentrationconcentrated under reduced pressure
2. dissolutionThe resulting residue was dissolved in 10% hydrochloric acid in methanol (50 mL)
3. temperatureThe mixture was refluxed for 18 h
4. concentrationconcentrated under reduced pressure
5. additionTo the suspension of resulting residue in dichloromethane (100 mL)
6. customThe organic layer was separated
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (1:1)

ORD record

ord-cc1ae520d04143c1b7375d52e1249d0f

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07906532B2