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

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).

1. washwith washing in N-methylpyrrolidone (36 ml)
2. distillationdistilled water (0.3 L)
3. washwashing thus extracted organic layer with a 5% by weight aqueous solution of potassium hydrogen sulfate (400 mL)
4. customTo residue obtained after concentration of the organic layer
5. stirringstirred over night at room temperature
6. filtrationCrystal generated was filtered
7. washwashed with ethanol (35 mL)

ORD record

ord-5b4e3d64f71d407c9b74987f1f6795a6

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07563893B2