Hydrochloric Acid → [2-(Methoxycarbonyl-phenyl-amino)-phenyl]-acetic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-phenyl-1,3-dihydro-indol-2-one (80 g, 382 mmol), sodium hydroxide (16.06 g, 402 mmol) and tetrahydrofuran (113 ml) is heated to reflux (67° C.) for S hours. The solution is diluted with another portion of tetrahydrofuran (169 ml) and cooled to −10° C. A 20% solution of butyllithium in cyclohexane (122.3 g, 382 mmol) is added at this temperature followed by dimethylcarbonate (51.7 g, 573 mmol). Afterwards, the solution is stirred at −10° C. for 2 hours. Concentrated hydrochloric acid (38 ml) and water (125 ml) are added and the organic solvents are distilled off at reduced pressure. After addition of toluene (345 ml) to the suspension, the pH of the water phase is adjusted to 1.5 using hydrochloric acid (34 ml). After phase separation at 75° C., the organic phase is washed with another portion of water (120 ml), concentrated at reduced pressure and allowed to crystallize at 0° C. to yield 81.2 g of pure title compound (75%).

Provenance & Evidence