Water → 6-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid

HRID 1095955Notes

Reaction equation

HRID 1095955 reaction equation
C[O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([CH:18]([CH3:32])[C:19]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=3)([OH:24])[C:20]([F:23])([F:22])[F:21])[CH:12]=2)=[N:6][CH:5]=1.[Li+].[OH-].O>C1COCC1>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:33])=[O:2])=[CH:5][N:6]=2)=[CH:12][C:13]=1[CH:18]([CH3:32])[C:19]([C:25]1[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=1)([OH:24])[C:20]([F:23])([F:21])[F:22]

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 723105956-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid methyl ester

Product 1

HCID 723105716-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid methyl ester (14 mg, obtained in Example 132) was dissolved in THF (5 mL). The mixture was cooled in an ice bath and aqueous LiOH solution (1.0 M, 0.048 mL) was added. The mixture was stirred over night at r.t. The reaction mixture was poured into water and extracted with ethyl acetate. The aqueous phase was acidified with 2 M aqueous HCl to pH 1 and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and the solvent was evaporated. The title compound was obtained as an off-white solid (12 mg, 88%) and was used without further purification. MS (neg. ion, m/e)=485.0 [(M−H)−].

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. extractionextracted with ethyl acetate
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated

Sources & evidence

ORD record
ord-258201d7d6904bb4bbcffa7fbd612d3a
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

Loading…