Formic Acid → (+)-3-(2,3-Difluorophenyl)-1-methylpyrrolidin-3-OL

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Reaction Steps

Preparation according to Example 11: Enantiomer E2 of 3-(2,3-difluorophenyl)pyrrolidin-3-ol (0.5 g, 2.5 mmol) in formic acid (7.2 mL) and aqueous formaldehyde (40%, 6.5 mL). 65° C. for 5 h. Water was added (50 mL), and the mixture was washed with diethyl ether. The water phase was basified with NaOH (5 M), extracted with ethyl acetate, dried (MgSO4) and evaporated. The crude compound was again treated with the same amount of formic acid and aqueous formaldehyde as above for 5 h. Purification by flash chromatography on silica gel (ethyl acetate/methanol, 4:1 to 2:1). Yield: 0.7 g. [α]D=−21.5° (methanol). The amine was converted to the oxalic acid salt and recrystallized from ethanol/diethyl ether: M.p. 134.3° C.; MS m/z (relative intensity, 70 eV) 213 (M+, 20), 58 (27), 141 (16), 127 (11), 57 (bp).

Provenance & Evidence