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

HRID 1427425Notes

Reaction equation

HRID 1427425 reaction equation
C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C@@H:11]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[CH2:12][CH:13]([CH3:15])[CH3:14])=[N:6][CH:5]=1.CO.[OH-].[Na+]>O1CCCC1>[CH3:14][CH:13]([CH3:15])[CH2:12][C@@H:11]([NH:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:32])=[O:2])=[CH:5][N:6]=1)[C:16]1[CH:17]=[CH:18][C:19]([C:22]2[CH:23]=[CH:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=2)=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 67980699(R)-methyl-6-(3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinate

Product 1

HCID 67981033(R)-6-(3-methyl-1-(4'-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinic acidYield 90.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customthe organic solvents removed under reduced pressure
  3. additionWater (300 mL) was added
  4. customA white precipitate formed
  5. stirringthe heterogeneous mixture was stirred for 30 minutes at 0° C
  6. filtrationThe mixture was then filtered
  7. customthe solid was dried under reduced pressure

Sources & evidence

ORD record
ord-90432d51bf354db58d0063856b002370
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

Loading…