Dimethylformamide → (5S,7S)-5-(N-(tert-butoxycarbonyl)-D-phenylalanyl)oxy-7-methyl-3-(3-trifluoromethylphenyl)-5,6,7,8-tetrahydrocinnoline

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Reaction Steps

To a N,N-dimethylformamide solution (181 mL) of 7-methyl-3-(3-trifluoromethylphenyl)-5,6,7,8-tetrahydrocinnolin-5-ol (27.8 g, 90.4 mmol) obtained in Example 6 were added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (26 g, 135.7 mmol) and N-(tert-butoxycarbonyl)-D-phenylalanine (31.2 g, 117.6 mmol) with washing in N-methylpyrrolidone (36 ml), followed by adding N,N-dimethylaminopyridine (1.2 mg, 9.0 mmol) to the mixed liquid under ice cooling, stirring over night, adding ethyl acetate (0.6 mL) and distilled water (0.3 L) and washing thus extracted organic layer with a 5% by weight aqueous solution of potassium hydrogen sulfate (400 mL), a saturated aqueous solution of sodium bicarbonate (300 mL) and a 10% saline solution (300 mL) sequentially. To residue obtained after concentration of the organic layer was added ethanol (187 mL) and stirred over night at room temperature. Crystal generated was filtered and washed with ethanol (35 mL) to obtain the titled objective compound (14.8 g).

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