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

HRID 1095952Notes

Reaction equation

HRID 1095952 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH:9]([CH3:23])[C:10]([C:16]1[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[CH:17]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].[CH3:24][O:25][C:26]1[CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:30][C:31]=1[C:32]([O:34][CH3:35])=[O:33].O>CC#N.CN(C)C1C=CN=CC=1>[CH3:35][O:34][C:32](=[O:33])[C:31]1[CH:30]=[CH:29][C:28]([O:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH:9]([CH3:23])[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[CH:17]=3)([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:4]=2)=[CH:27][C:26]=1[O:25][CH3:24]

Participants

6

Reactant 3

HCID 962WaterHCID 22171502Methyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 252546034-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenol

Product 1

HCID 595087194-{4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-methoxy-benzoic acid methyl esterYield 33%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

4-Chloro-3-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenol (50 mg) was dissolved in CH3CN (2 mL). To this solution was added 3-methoxy-4-methoxycarbonyl-phenylboronic acid pinacol ester (120 mg, [CAS Reg. No. 603122-40-3]), cupric(II)-acetate (74.5 mg) and 4-dimethylaminopyridine (66.7 mg). The rection mixture was stirred at 80° C. for 18 hours. The mixture was cooled, poured into water, extracted with ethyl acetate and the organic layer was washed with brine, dried over Na2SO4 and evaporated. The residue was purified by amino phase chromatography (ethyl acetate:heptane=2:3) to give the desired compound as a colorless solid (24 mg, 33%). MS (neg. ion, m/e)=527.9 [(M−H)−].

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with ethyl acetate
  3. washthe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe residue was purified by amino phase chromatography (ethyl acetate:heptane=2:3)

Sources & evidence

ORD record
ord-c07a8f4174ba4e48b1da8dbe612f6894
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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