Phthalimide, N-(2-formylethyl)- → Ethyl 3-{[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

Participants

Reaction Steps

A solution of ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (1.00 g, 3.65 mmol) and 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanal (0.929 g, 4.57 mmol) under nitrogen in glacial acetic acid (10 mL) was treated with sodium triacetoxyborohydride (1.55 g, 7.31 mmol) at ambient temperature. After stirring for 20 min., the reaction was evaporated in vacuo and the residue was partitioned between EtOAc and 5% w/v aq. K2CO3. After separating the layers, the aqueous phase was diluted with sat. aq. NaCl and back-extracted with EtOAc. The combined organic layers were washed with sat. aq. NaCl, dried over MgSO4, filtered and evaporated in vacuo. The residue was dissolved in warm Et2O leaving a small residue of insolubles. The Et2O was decanted and evaporated to approximately half volume where precipitation occurred. The product was collected by filtration and dried under high vacuum: 1H NMR (d6-DMSO) δ 7.78-7.86 (4H, m), 7.73 (1H, s), 7.65 (1H, t, J=7 Hz), 7.25-7.30 (2H, m), 7.06-7.12 (3H, m), 4.18 (2H, q, J=7 Hz), 3.90 (2H, s), 3.65 (2H, t, J=6 Hz), 3.24 (2H, q, J=5 Hz), 1.80-1.89 (2H, m), 1.24 (3H, t, 7 Hz); ES+ MS: 462 (M+H+).

Provenance & Evidence