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

HRID 975676Notes

Reaction equation

HRID 975676 reaction equation
CC(C)([O-])C.[K+].[C:7]([SH:15])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:16]([O:19][C:20]([N:22]1[CH2:26][C@H:25](OS(C)(=O)=O)[CH2:24][C@H:23]1[CH2:32][CH2:33][N:34]1[CH:38]=[CH:37][N:36]=[C:35]1[C:39](=[O:41])[NH2:40])=[O:21])[CH:17]=[CH2:18]>CN(C)C=O>[CH2:16]([O:19][C:20]([N:22]1[CH2:26][C@@H:25]([S:15][C:7](=[O:14])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:24][C@H:23]1[CH2:32][CH2:33][N:34]1[CH:38]=[CH:37][N:36]=[C:35]1[C:39](=[O:41])[NH2:40])=[O:21])[CH:17]=[CH2:18]

Participants

5

Reactant 3

HCID 7414Thiobenzoic AcidHCID 23665647Potassium tert-butoxideHCID 54523979(2R,4R)-1-allyloxycarbonyl-2-{2-(2-carbamoylimidazol-1-yl) ethyl}-4-methylsulfonyloxypyrrolidine

Product 1

HCID 57258433(2R,4S)-1-allyloxycarbonyl-4-benzoylthio-2-[2-(2-carbamoylimidazol-1-yl) ethyl]pyrrolidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-1eefc0badb46430a9763e2b7e21ed8fd
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

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