Lithium Hydroxide → 3-Methyl-1,2-oxazole-5-carbonyl chloride

Participants

Reaction Steps

(±)-trans-2-Methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide was made following general procedure A, substituting 3-methyl-isoxazole-5-carbonyl chloride for 4-trifluoromethyl-benzoyl chloride. 3-Methyl-isoxazole-5-carbonyl chloride was prepared by reaction of the preformed 3-methyl-isoxazole-5-carboxylic acid with oxalyl chloride and dimethylformamide in methylene chloride. In addition, only 1.2 equivalents of lithium hydroxide were used in the ester hydrolysis step. The crude 2-methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide was isolated as a mixture of cis and trans isomers. Purification by silica gel chromatography (dichloromethane/methanol gradient: 99.5/0.5->99/1) yielded (±)-trans-methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (24%). 1H-NMR (CDCl3) δ: 1.02 (t, 3H), 1.13 (d, 3H), 1.40-1.50 (m, 1H), 2.25 (s, 3H), 2.70-2.80 (m, 1H), 3.40-3.52 (m, 1H), 3.80 (q, 2H), 4.95-5.10 (m, 1H), 6.35 (d, 1H), 6.42 (s, 1H), 6.70 (d, 1H), 6.90 (t, 1H), 7.00 (t, 1H), 7.10 (d, 2H), 7.40 (d, 2H). MS m/z: 438/440 (M+1).

Provenance & Evidence