Chloroacetic Acid → 4-Chloro-2-(2-chloro-ethylamino)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid methyl ester

Participants

Reaction Steps

Sodiumborohydride (1.77 g, 46.78 mmol) was added portionwise to a stirred solution of chloro-acetic acid (7.71 g, 81.59 mmol) in benzene (270 mL) and dry tetrahydrofuran (30 mL) under nitrogen atmosphere at 15° C. The reaction mixture was stirred for 1 h, treated with the methyl ester of Example 35j (5 g, 13.61 mmol) and refluxed for 0.5 h. The reaction mixture was treated with 10% aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with water, brine, dried, concentrated and purified by crystallization (ethyl acetate/hexane) to obtain the title compound as a white solid. Yield: 5.25 g, (90%); mp: 224-225° C.; 1H NMR (DMSO-d6): δ 2.71 (s, 3H, CH3), 3.45 (t, 2H, CH2), 3.75 (t, 2H, CH2), 3.92 (s, 3H, OCH3), 5.15 (s, 2H, CH2), 6.53 (t, 1H, NH), 6.65-6.79 (m, 2H, Ar), 8.10 (s, 1H, Ar), 8.15 (s, 1H, Ar). MS: m/e (ES+) 431 (M+1).

Provenance & Evidence