Hydrochloric Acid → 8-(2-Chlorophenyl)-6-methyl-1,8-dihydropyrido [2,1-c][1,4]-oxazine-7,9-dicarboxylic acid 9-ethyl 7-methyl ester

Participants

Reaction Steps

To a solution of 4-(2-chlorophenyl)-2-(2,2-dimethoxy-ethoxymethyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (XX, 9.2 g) in tetrahydrofuran (200 mL) was added 3N hydrochloric acid (40 mL). The mixture was then refluxed for 4 h. On cooling to room temperature, tetrahydrofuran was removed under reduced pressure and the residue taken up in ethyl acetate (200 mL). The organic phase was washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a solvent mixture of hexane and ethyl acetate as eluent (90:10; 1L) as eluent to afford the title compound (XXI 5.2 g). 1H-NMR (CDCl3) δ (ppm): 1.22 (t, 3H, J=7.1 Hz), 2.43 (s, 3H), 3.68 (s, 3H), 4.12 (q, 2H, J=7. 1 Hz),4,60(d,1H, J=13.5 Hz), 5.48 (s, 1H), 5.70 (d, 1H, J=13.8 Hz), 6.21 (d, 1H, J=4.7 Hz), 6.30(d, 1H, J=4.6 Hz), 7.07-7.28 (m, 4H); 13C-NMR (CDCl3) δ (ppm): 14.1, 15.7, 36.6, 51.2, 60.6, 63.5, 105.8, 106.7, 107.8, 127.3, 127.8, 129.5, 130.4, 131.8, 132.5 139.2, 142.0, 143.4, 166.4, 168.1; HRMS: calc. for C20H20CIN2O5 389.1030 found 389.1020; Elemental Analysis (%): calc. (found) C 61.62 (61.78), H 5.17 (5.27), N 3.59 (3.51); M.p. 126.0°-126.8° C.; IR (KBr, cm-1): 1693, 1662, 1645, 1581.

Provenance & Evidence