Potassium Carbonate → HCID 58732756, compound

Participants

Reaction Conditions

Reaction Steps

(±)-trans-1-(4-Hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (585 mg, 1.30 mmol) was dissolved in dimethylformamide (20 mL). Potassium carbonate (1.5 g) was added, followed by ethyl-4-bromobutyrate (2.53 g, 1.9 mL, 13 mmol). The reaction was warmed to 90° C. and stirred under nitrogen overnight. Upon completion, the reaction was cooled to room temperature. The solvent layer was decanted and concentrated. The residue was dissolved in ethyl acetate. The residual solids in the reaction flask were washed with ethyl acetate and the washings combined with the filtrate ethyl acetate solution. The combined ethyl acetate layers were washed with water (3×) and brine, dried over sodium sulfate, filtered, and concentrated to afford the crude product. The crude material was a mixture of cis and trans isomers due to racemization under the alkylation conditions. The mixture was purified by silica gel chromatography (ethyl acetate/hexanes gradient) to afford pure (±)-trans-4-(4-{4-[(4-chloro-phenyl)-ethyl-carbamoyl]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid ethyl ester as a foam (88%) and pure (±)-cis-4-(4-{4-[(4-Chloro-phenyl)-ethyl-carbamoyl]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid ethyl ester. Data for the trans isomer: 1H-NMR (CDCl3) δ: 0.97 (d, 3H), 1.13 (t, 3H), 1.24 (t, 3H), 1.73 (ddd, 1H), 2.01-2.14 (m, 2H), 2.41-2.59 (m, 3H), 3.61-4.00 (m, 5H), 4.06-4.18 (m, 2H), 5.01-5.14 (m, 1H), 6.44 (d, 1H), 6.68-6.84 (m, 4H), 6.89 (dd, 1H), 7.16-7.27 (m, 2H), 7.42-7.51 (m, 4H). MS m/z: 563 (M+1).

Provenance & Evidence