(Diethylamino)sulfur trifluoride → (3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

Process A: (3R,4R)-3-Azidomethyl-1-benzyloxycarbonyl-4-hydroxypyrrolidine (1.20 g) was dissolved in dichloromethane (40 mL). While this solution was chilled in a salt/ice bath, diethylaminosulfur trifluoride (1.20 mL) was added dropwise and the mixture was stirred at room temperature for 3 hours. The reaction vessel was again chilled in a salt/ice bath, followed by dropwise addition of a second portion of diethylaminosulfur trifluoride (0.57 mL) and stirring at room temperature for 2 hours. While the reaction mixture was kept chilled in the ice bath, a saturated aqueous solution of sodium bicarbonate (40 mL) was added dropwise and the dichloromethane layer was separated. The dichloromethane layer was then washed with a saturated aqueous solution of sodium bicarbonate (2×20 mL) and then water (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: hexane: ethyl acetate=2:1) to give (3R,4S)-3-azidomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a pale brown oil (726 mg).

1. additionwas added dropwise
2. temperatureThe reaction vessel was again chilled in a salt/ice bath
3. stirringstirring at room temperature for 2 hours
4. customthe dichloromethane layer was separated
5. washThe dichloromethane layer was then washed with a saturated aqueous solution of sodium bicarbonate (2×20 mL)
6. dry with materialwater (20 mL), dried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe resulting residue was purified by silica gel column chromatography (eluant: hexane: ethyl acetate=2:1)

ORD record

ord-a4c087e9c1ef4720acef81a78cd0e27f

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07514451B2