Hydrochloric Acid → Ethyl 6-chloro-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate

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반응 단계

A solution of the crude product of 6-chloro-5-(ethoxycarbonyl)-1H-indole-2-carboxylic acid (1.9 g) from Synthesis Example 1, Stage 2 and 2,2,2-trifluoro-1-[3-trifluoromethylphenyl]ethanamine (1.12 g, 4.60 mmol) (lit. DE 2723464) in N,N-dimethylformamide (15 ml) was admixed with 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (953 mg, 4.60 mmol), and the mixture was stirred at room temperature for 4 days. The reaction solution was admixed with hydrochloric acid (1 M) and extracted with ethyl acetate. The organic phase was washed with sat. sodium hydrogencarbonate solution and saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. Column chromatography purification on silica gel with cyclohexane/ethyl acetate as the eluent (gradient from 10% ethyl acetate to 25% ethyl acetate) gave 603 mg (26% of theory over 2 stages) of ethyl 6-chloro-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate.

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