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

HRID 2096854Notes

Reaction equation

HRID 2096854 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:41])[C:30]1[C:35]([C:36]([F:39])([F:38])[F:37])=[CH:34][C:33](Cl)=[N:32][CH:31]=1.C(N(CC)CC)C.N12CCN(CC1)CC2>CN(C)C(=O)C.CCOC(C)=O.O>[CH3:27][O:28][C:29](=[O:41])[C:30]1[C:35]([C:36]([F:37])([F:38])[F:39])=[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

8

Reactant 4

HCID 8471TriethylamineHCID 9237DabcoHCID 2775340Methyl 6-chloro-4-(trifluoromethyl)nicotinateHCID 666970264-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-2,6-dimethyl-benzonitrile

Product 1

HCID 723101226-{3-Chloro-4-[2-(4-cyano-3,5-dimethyl-phenyl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-4-trifluoromethyl-nicotinic acid methyl esterYield 86.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 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 (1 ml) were added methyl-6-chloro-4-(trifluoromethyl)-nicotinate (75 mg), triethylamine (34 mg) and 1,4-diazabicyclo[2.2.2]octane (4 mg). The mixture was stirred at room temperature for 6 h 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 (132 mg) as a colorless solid. MS (m/e, ISP neg. ion)=585.1 [M−H+].

Workup

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

Sources & evidence

ORD record
ord-5f7f3af30d0d45b3a3234b3bd58fbbf3
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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