Water → 6-{3-Chloro-4-[2-(4-cyano-3,5-dimethyl-phenyl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid methyl ester

HRID 2096855Notes

Reaction equation

HRID 2096855 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:26])[C:10]([C:16]1[CH:23]=[C:22]([CH3:24])[C:19]([C:20]#[N:21])=[C:18]([CH3:25])[CH:17]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].[CH3:27][O:28][C:29](=[O:37])[C:30]1[CH:35]=[CH:34][C:33](Cl)=[N:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C(=O)C.CCOC(C)=O>[CH3:27][O:28][C:29](=[O:37])[C:30]1[CH:35]=[CH:34][C:33]([O:8][C:6]2[CH:5]=[CH:4][C:3]([CH:9]([CH3:26])[C:10]([C:16]3[CH:17]=[C:18]([CH3:25])[C:19]([C:20]#[N:21])=[C:22]([CH3:24])[CH:23]=3)([OH:15])[C:11]([F:14])([F:12])[F:13])=[C:2]([Cl:1])[CH:7]=2)=[N:32][CH:31]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 254249Methyl 6-chloropyridine-3-carboxylate2×HCID 666970264-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-2,6-dimethyl-benzonitrile

Product 1

HCID 666970286-{3-Chloro-4-[2-(4-cyano-3,5-dimethyl-phenyl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-nicotinic acid methyl esterYield 76.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 4-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-2,6-dimethyl-benzonitrile (Example 141, step 5, 100 mg) in N,N-dimethylacetamide (2 ml) were added methyl-6-chloro-nicotinate (68 mg) and cesium carbonate (256 mg). The mixture was stirred at room temperature for 3 h. Methyl-6-chloro-nicotinate (23 mg) was added and the mixture was stirred overnight and then diluted with EtOAc. Water was added. The mixture was extracted with EtOAc. The organic phase was washed with water, dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>2:3) to give the title compound (103 mg) as a colorless solid. MS (m/e)=519.2 [M+H+].

Workup

  1. stirringthe mixture was stirred overnight
  2. extractionThe mixture was extracted with EtOAc
  3. washThe organic phase was washed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>2:3)

Sources & evidence

ORD record
ord-892b272a1bb6447fbadd5cd43a438cbd
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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