Hydrochloric Acid → tert-butyl (3R,4S)-4-hydroxy-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate

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Reaction Steps

To a solution of benzyl (3R,4S)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)-4-hydroxypyrrolidin-3-ylcarbamate (1.16 g, 2.7 mmol) in acetonitrile (2 mL) cooled to 0° C. in an ice bath was added iodotrimethylsilane (1.22 mL, 8.10 mmol) and the mixture allowed to warm to ambient temperature for 1 hour. The reaction mixture was poured into aqueous 1N HCl (15 mL) and stirred for 10 minutes and extracted with diethyl ether. The aqueous layer was pH adjusted to 10 with a 5N sodium hydroxide solution and extracted with ethyl acetate. The organic extract was dried (MgSO4), filtered and concentrated under reduced pressure. The residue (0.512 g, 1.29 mmol) was combined with anhydrous hydrazine (0.81 mL, 25.87 mmol) in i-BuOH (3 mL) in a sealed tube and heated with stirring at 100° C. for 18 hours. After cooling, the mixture was partitioned between water (15 mL) and ethyl acetate (50 mL). The layers were separated and the organic layer was washed with saturated sodium bicarbonate and brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford tert-butyl (3R,4S)-4-hydroxy-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (0.44 g, 86%).

Provenance & Evidence