Ethyl Acetate → (2R,4S)-N-allyloxycarbonyl-2-(2-oxopyrrolidin-3-ylmethyl)-4-tritylthiopyrrolidine

Lithium diisopropylamide (2.1M tetrahydrofuran solution, 6.45 ml, 13.5 mmol) was dropwise added to a solution of N-tert-butyldimethylsilyl-2-oxopyrrolidine (1.80 g, 9.03 mmol) in tetrahydrofuran (150 ml) at -78° C., and the mixture was stirred at the same temperature for 15 minutes. Then, a solution of (2S,4S)-N-allyloxycarbonyl-2-iodomethyl-4-tritylthiopyrrolidine (2.57 g, 4.5 mmol) in tetrahydrofuran (18 ml) was dropwise added thereto, and the mixture was stirred at the same temperature for 1 hour. The reaction solution was poured into a mixture of ethyl acetate (150 ml) and a 10% ammonium chloride aqueous solution (50 ml) for liquid separation. The organic layer was washed sequentially with a 10% sodium dihydrogen phosphate aqueous solution (100 ml) and a saturated sodium chloride aqueous solution (100 ml), then dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in tetrahydrofuran (12 ml) and methanol (3 ml), and 6N hydrochloric acid (3 ml) was added thereto under cooling with ice. The mixture was stirred for 1 hour. Ethyl acetate (50 ml) was added to the reaction solution, and the organic layer was washed sequentially with a saturated sodium hydrogen carbonate aqueous solution (30 ml) and a saturated sodium chloride aqueous solution (30 ml), then dried over anhydrous sodium sulfate and concentrated. The residue was subjected to silica gel flash column chromatography (Wakogel™ C-300, 40 ml, ethyl acetate-n-hexane 3:1) to obtain (2R,4S)-N-allyloxycarbonyl-2-(2-oxopyrrolidin-3-ylmethyl)-4-tritylthiopyrrolidine (880 mg, yield: 37%).

1. stirringthe mixture was stirred at the same temperature for 1 hour
2. customa 10% ammonium chloride aqueous solution (50 ml) for liquid separation
3. washThe organic layer was washed sequentially with a 10% sodium dihydrogen phosphate aqueous solution (100 ml)
4. dry with materiala saturated sodium chloride aqueous solution (100 ml), then dried over anhydrous sodium sulfate
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in tetrahydrofuran (12 ml)
7. additionmethanol (3 ml), and 6N hydrochloric acid (3 ml) was added
8. temperatureunder cooling with ice
9. stirringThe mixture was stirred for 1 hour
10. additionEthyl acetate (50 ml) was added to the reaction solution
11. washthe organic layer was washed sequentially with a saturated sodium hydrogen carbonate aqueous solution (30 ml)
12. dry with materiala saturated sodium chloride aqueous solution (30 ml), then dried over anhydrous sodium sulfate
13. concentrationconcentrated

ORD record

ord-d0c8f092e98842eab9ec12ac4e840b93

Source dataset

uspto-grants-1994_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05374720