Imidazole → (S)-(S)-3-Oxiranylpyrrolidine-1-carboxylic Acid t-Butyl Ester

Temperature

0 °C

(S)-34S)-1,2-Dihydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester (230 g, 990 mmol, 1.0 eq.) was combined with MeTHF (4.9 kg, 57 mol) and cooled to 0° C. 2.0 M Sodium t-butoxide in THF (994 mL, 2.0 eq.) was added drop wise over 20 minutes. The mixture was stirred at −1° C. for 15 minutes, then cooled to −7° C. p-Tolylsulfonyl)imidazole (243 g, 1.1 mol, 1.1 eq.) was added and the resulting mixture was stirred at 0° C. for 2 hours. The reaction was quenched with cold H2O (5.7 kg, 320 mol). Hexanes (1.8 kg, 21 mol) was added and the mixture was warmed to 23° C. and stirred for about 30 minutes. The layers were allowed to settle, the phases were separated, and the reaction vessel was rinsed with MeTHF (100 mL). The organic layer (˜8 L) was removed and stored at 5° C. overnight, then filtered through Na2SO4 and concentrated at 60 torr to 30 torr with a water bath at 25° C. to yield the title compound (220 g).

1. additionwas added
2. stirringthe resulting mixture was stirred at 0° C. for 2 hours
3. temperaturethe mixture was warmed to 23° C.
4. stirringstirred for about 30 minutes
5. customthe phases were separated
6. washthe reaction vessel was rinsed with MeTHF (100 mL)
7. customThe organic layer (˜8 L) was removed
8. waitstored at 5° C. overnight
9. filtrationfiltered through Na2SO4
10. concentrationconcentrated at 60 torr to 30 torr with a water bath at 25° C.

ORD record

ord-9141bc28d9bd4e6c8d72243c13c3942a

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658691B2