Thiobenzoic Acid → (2R,4S)-1-allyloxycarbonyl-4-benzoylthio-2-[2-(2-carbamoylimidazol-1-yl) ethyl]pyrrolidine

To a solution of potassium t-butoxide (8.42 g) in dimethylformamide (70 ml) was added thiobenzoic S-acid (9.27 ml) dropwise at -20° C. under dry ice--acetone bath. After the addition, the solution was warmed to room temperature, and then stirred for 75 minutes. To the solution was added a solution of (2R,4R)-1-allyloxycarbonyl-2-[2-(2-carbamoylimidazol-1-yl)ethyl]-4-methylsulfonyloxypyrrolidine (14.5 g) in dimethylformamide (70 ml) and the mixture was heated to 85° C. and stirred for 2 hours. After cooling to room temperature, the mixture was quenched by the addition of water (280 ml) and extracted with ethyl acetate (140 ml×3). The combined extract was washed with aqueous saturated sodium bicarbonate solution (140 ml×2), water (200 ml×2), and brine (200 ml×2), and then dried over magnesium sulfate. The solvent was evaporated and the residue was chromatographed on a 150 g of silica gel eluting with a mixture of chloroform and methanol (95:5, V/V) to give (2R,4S)-1-allyloxycarbonyl-4-benzoylthio-2-[2-(2-carbamoylimidazol-1-yl) ethyl]pyrrolidine (11.2 g) as a yellow paste.

1. additionAfter the addition
2. temperaturethe mixture was heated to 85° C.
3. stirringstirred for 2 hours
4. temperatureAfter cooling to room temperature
5. customthe mixture was quenched by the addition of water (280 ml)
6. extractionextracted with ethyl acetate (140 ml×3)
7. extractionThe combined extract
8. washwas washed with aqueous saturated sodium bicarbonate solution (140 ml×2), water (200 ml×2), and brine (200 ml×2)
9. dry with materialdried over magnesium sulfate
10. customThe solvent was evaporated
11. customthe residue was chromatographed on a 150 g of silica gel eluting with a mixture of chloroform and methanol (95:5, V/V)

ORD-Eintrag

ord-1eefc0badb46430a9763e2b7e21ed8fd

Quelldatensatz

uspto-grants-1997_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05608056