Methanol → (R)-6-(3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinic acid

Participants

Reaction Conditions

Reaction Steps

A round bottom flask was charged with (R)-methyl-6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinate (41.5 g, 93.8 mmol), methanol (200 mL) and tetrahydrofuran (200 mL). 1.0N NaOH (188 mL) was then added and the resulting solution was stirred at 50° C. for 3 hours. The reaction was cooled to room temperature and the organic solvents removed under reduced pressure. Water (300 mL) was added and the mixture was acidified with 10% citric acid to pH=3. A white precipitate formed and the heterogeneous mixture was stirred for 30 minutes at 0° C. The mixture was then filtered and the solid was dried under reduced pressure to afford (R)-6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinic acid (36.2 g, 90.0%). 1H NMR (400 MHz, CDCl3, δ): 0.98 (d, J=6.46 Hz, 3H) 1.03 (d, J=6.46 Hz, 3H) 1.66-1.78 (m, 1H) 1.78-1.89 (m, 1H) 1.96-2.05 (m, 1H) 4.49-4.63 (m, 1H) 6.44 (d, J=9.00 Hz, 1H) 7.44-7.50 (m, 2H) 7.53-7.58 (m, 2H) 7.63-7.70 (m, 4H) 8.17 (d, J=9.19 Hz, 1H) 8.69-8.74 (m, 1H) 9.44 (br. s., 1H). MS (M+1): 429.4.

Provenance & Evidence