Sodium triacetoxyborohydride → Ethyl 5-(4-fluorobenzyl)-3-{[2-(2-oxopyrrolidin-1-yl)ethyl]amino}pyridine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

(2-Oxopyrrolidin-1-yl)acetaldehyde (2.00 g, 15.7 mmol) and ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (2.00 g, 7.32 mmol) were combined in 1:1 dichloroethane/acetic acid (10 mL) and cooled under nitrogen to 0-5° C. Sodium trisacetoxyborohydride (3.10 g, 14.6 mmol) was added and the reaction was stirred for 15 min. Two additional portions of aldehyde (1.0 g, 7.8 mmol) plus sodium triacetoxyborohydride (1.65 g, 7.8 mmol) separated by 15 min. increments were made. The reaction mixture was evaporated in vacuo, dissolved in CH2Cl2, and treated with aqueous K2CO3 (5% w/v). After separating the layers, the aqueous phase was back-extracted twice with CH2Cl2. The combined organic phases were dried over MgSO4, filtered, evaporated in vacuo and purified on silica gel eluting with 0-3% MeOH in EtOAc to provide an oil: 1H NMR (CDCl3) δ 7.89 (1H, d, J=1.4 Hz), 7.83 (1H, br t, J˜6 Hz), 7.15 (2H, dd, J˜9, 6 Hz), 6.98 (2H, t, J˜9 Hz), 6.92 (1H, s), 4.42 (2H, q, J=7 Hz), 3.92 (2H, s), 3.49 (2H, m), 3.41 (2H, t, J=7 Hz), 3.35 (2H, q, J=6 Hz), 2.36 (2H, t, J=8 Hz), 1.99 (2H, m), 1.42 (3H, t, J=7 Hz); ES+ MS: 386 (M+H+).

Provenance & Evidence