Triethylamine → (S)-4-Chloro-2-fluorobenzyl-[1-(6-fluoropyridin-3-yl)-pyrrolidin-3-yl]-amine

Participants

Reaction Steps

Dissolve 1-(6-fluoropyridin-3-yl)-pyrrolidin-3-ylamine hydrochloride (43 mg, 0.20 mmol) in methanol (1 mL). Add triethylamine (90 μL, 0.65 mmol) and 4-chloro-2-fluorobenzaldehyde (35 mg, 0.22 mmol), vortex and let sit overnight at room temperature. Add sodium borohydride (15 mg, 0.39 mmol) and let sit 1 h. Dilute the mixture with methanol and pour onto a column of Dowex® 50wx4-200 (1.5 g). Wash with methanol and discard the washing, then elute with 5% triethylamine in methanol. Concentrate to give the title compound as a residue. Dissolve the residue in methanol and add 1 N HCl in methanol (0.75 mL). Concentrate and dry in vacuum oven at 50° C. overnight to give the title compound as its hydrochloride salt (53 mg, 74%). 1H NMR (400 MHz, MeOH-d4) δ 7.63 (t, 1H, J=8.0 Hz), 7.58-7.57 (m, 1H), 7.45 (dd, 1H, J=9.6, 2.0 Hz), 7.40 (dd, 1H, J=8.0, 2.0 Hz), 7.36-7.32 (m, 1H), 7.00 (dd, 1H, J=8.8, 2.8 Hz), 4.44 (s, 2H), 4.21-4.15 (m, 1H), 3.74-3.61 (m, 3H), 3.42-3.36 (m, 1H), 2.68-2.60 (m, 1H), 2.38-2.29 (m, 1H), MS (ES): m/z=324 [M+H].

Provenance & Evidence