Methyl 3-(6-(3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butoxy)nicotinamido)propanoate → (+/-)-3-(6-(3-Methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butoxy)nicotinamido)propanoic acid
Reaction equation
[CH3:1][CH:2]([CH3:37])[CH2:3][CH:4]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)[O:5][C:6]1[CH:20]=[CH:19][C:9]([C:10]([NH:12][CH2:13][CH2:14][C:15]([O:17]C)=[O:16])=[O:11])=[CH:8][N:7]=1>O1CCCC1.O>[CH3:1][CH:2]([CH3:37])[CH2:3][CH:4]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[CH:29][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:31][CH:32]=2)=[CH:23][CH:22]=1)[O:5][C:6]1[CH:20]=[CH:19][C:9]([C:10]([NH:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[O:11])=[CH:8][N:7]=1Participants
4
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of methyl 3-(6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butoxy)nicotinamido)propanoate (0.40 g, 0.77 mmol) in tetrahydrofuran (5 mL) was added a solution of LiOH monohydrate (326 mg, 7.77 mmol) in water (5 mL). The mixture was stirred at room temperature overnight. Tetrahydrofuran was removed under reduced pressure and the aqueous residue was acidified to pH=3 by addition of 1N HCl. The mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Purification by HPLC (column: Phenomenex Gemini 200×21.2 mm, 10 μm; modifier: ammonium hydroxide (to pH 10); gradient: 28 to 50% acetonitrile in water) gave (+/−)-3-(6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butoxy)nicotinamido)propanoic acid (30 mg) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.49-8.53 (m, 1H), 8.0-8.05 (m, 1H), 7.77 (d, 2H), 7.72 (d, 2H), 7.61 (d, 2H), 7.49 (d, 2H), 6.88 (d, 1H), 6.25-6.20 (m, 1H), 3.50-3.55 (m, 2H), 2.50-2.40 (m, 2H), 2.08-2.02 (m, 1H), 1.80-1.63 (m, 2H), 1.01-0.96 (m, 6H). MS (M+Na): 523.5.