Ethyl Acetate → HCID 67244304, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 14.5 g (51.9 mmol) of methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylate, 31.6 g (104 mmol) of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole and 21.5 g (156 mmol) of K2CO3 in 100 mL of DMF was stirred at 50° C. for 20 hr. Additional 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole (15.8 g, 52 mmol), DMF (50 mL), and K2CO3 (14.5 g, 105 mmol) was added and the reaction was heated for an additional 7 hours at 70° C. and at 60° C. for another 12 hours. The reaction was allowed to cool to room temperature and was stirred for 2 days. EtOAc was added then the mixture washed with three portions of H2O, then brine. The aqueous layers were extracted with EtOAC. The combined organic layers were dried over Na2SO4, filtered, then concentrated. The crude material was dissolved in hot EtOAc and diluted with hexane. The mixture was placed in the freezer for three hours then filtered to yield the desired product (14.46 g) as a light brown solid. The filtrate was concentrated and the residue purified by silica gel chromatography (330 g of silica gel eluting with 0-80% EtOAc in hexanes over 45 minutes). Fractions containing the product were combined, concentrated, and recrystallized to give 16.82 g (59%) of methyl 7-[4-({[3-(2-chlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-isoquinolinecarboxylate. 1H NMR (400 MHz, CDCl3): δ 9.35 (s, 1H), 8.60 (s, 1H), 8.14 (s, 1H), 7.99 (m, 2H), 7.60 (d, J=9 Hz, 2H), 7.41 (d, J=9 Hz, 2H), 7.33 (m, 1H), 6.92 (d, J=9 Hz, 2H), 4.80 (s, 2H), 4.06 (s, 3H), 3.36 (septet, 1H, J=7 Hz), 1.44 (d, J=7 Hz, 6H). ESI-LCMS m/z 548 (M+H)+.

Provenance & Evidence