Sodium Carbonate → 3-(3-Chloro-5-fluorophenyl)-1-methylpyrrolidin-3-ol

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Reaction Conditions

Reaction Steps

A mixture of 3-(3-chloro-5-fluorophenyl)pyrrolidin-3-ol (0.4 g, 1.85 mmol) in formic acid (5.4 mL) and aqueous formaldehyde (40%, 4.8 mL) was heated at 85° C. for 2.5 h. Aqueous sodium carbonate (10%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (2×70 mL), the combined organic phase was dried (MgSO4) and evaporated. Purification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 20:80 to 100:0) gave the title compound (0.131 g). The amine was converted to the fumaric acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 129-131° C.; MS m/z (relative intensity, 70 eV) 229 (M+, 7), 157 (5), 129 (6), 58 (30), 57 (bp).

Provenance & Evidence