3-Nitrobenzaldehyde → Nimodipine

Participants

Reaction Steps

A solution of 2-methoxyethyl acetoacetate (51) (32 g, 0.2 mol), 1-methylethyl 3-aminocrotonate (52) (28.8 g, 0.2 mol) and 3-nitrobenzaldehyde (30.6 g, 0.2 mol) in 2-propanol (280 mL) was refluxed for 9 h. The mixture was diluted with dichloromethane (1000 mL) and dried (MgSO4), and the solvent was removed with a rotary evaporator. The crude produce was recrystallized from ethyl acetate-petroleum ether to afford 48 g (0.115 mol, 58%) of 50 as a yellow crystalline solid: mp 122°-123° C. (lit.81 mp 125° C.); IR (CH2Cl2) 3440, 2975, 1692, 1620, 1530, 1460, 1345, 1210, 1095 cm-1 ; 1H NMR (CDCl3) δ 1.08 (d, J=6.2 Hz, 3H), 1.25 (d, J=6.2 Hz, 3H), 2.33 (s, 6H), 3.33 (s, 3H), 3.55 (t, J=4.8 Hz, 2H), 4.12-4.20 (m, 2H), 4.93 (septet, J=6.2 Hz, 1H), 5.09 (s, 1H), 6.31 (s, 1H), 7.34-8.13 (m, 4H); 13C NMR (CDCl3) δ 19.38, 19.53, 21.85, 22.17, 40.14, 58.90, 63.05, 67.43, 70.58, 102.93, 103.75, 121.36, 123.33, 128.70, 134.81, 144.84, 145.62, 148.16, 150.20, 166.75, 167.26.

Provenance & Evidence