proline dl-form → Ethyl 3-(4-chloro-2-methylphenyl)-3-{7-[(ethylsulfanyl)methyl]-1H-indol-3-yl}propanoate

Participants

Reaction Steps

849 mg (5.49 mmol) of 4-chloro-2-methylbenzaldehyde, 791 mg (5.49 mmol) of Meldrum's acid and 30.1 mg (0.26 mmol) of D,L-proline were added to a solution of 1.00 g (5.23 mmol) of the compound from Example 10A in 44 ml of acetonitrile. The reaction mixture was stirred at RT overnight. It was concentrated, the residue was taken up in diethyl ether, and a precipitate was separated off and discarded. Concentration resulted in 2.70 g of a crude product, of which 2.40 g were introduced into 9.5 ml of pyridine and 2.5 ml of ethanol, and 0.9 mg (14 μmol) of copper powder was added. The reaction mixture was heated under reflux for 1 h. It was concentrated, and the residue was taken up in ethyl acetate, washed with 1N hydrochloric acid, dried over magnesium sulfate, filtered through silica gel and concentrated. 950 mg of a crude product were obtained and were introduced into 14.2 ml of pyridine and 3.7 ml of ethanol, and 1.3 mg (21 μmol) of copper powder were added. The reaction mixture was heated under reflux for 1 h. It was concentrated, and the residue was taken up in ethyl acetate, washed with 1N hydrochloric acid, dried over magnesium sulfate, filtered through silica gel and concentrated. The crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient) to result in 620 mg of the title compound.

Provenance & Evidence