Triethylamine → 5-(2-Chloro-5-trifluoromethyl-phenyl)-6-cyclopentyloxy-3-pyridinecarboxylic acid methyl ester

HRID 1766437Notes

Reaction equation

HRID 1766437 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[C:9](Br)[CH:10]=1)=[O:4].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=1B(O)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[C:9]([C:20]2[CH:21]=[C:22]([C:25]([F:27])([F:28])[F:26])[CH:23]=[CH:24][C:19]=2[Cl:18])[CH:10]=1)=[O:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 27826702-Chloro-5-(trifluoromethyl)phenylboronic acidHCID 66844699Methyl 5-bromo-6-(cyclopentyloxy)nicotinate

Product 1

HCID 675053545-(2-Chloro-5-trifluoromethyl-phenyl)-6-cyclopentyloxy-3-pyridinecarboxylic acid methyl esterYield 61.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

5-Bromo-6-cyclopentyloxy-3-pyridinecarboxylic acid methyl ester (0.33 g, 1.1 mmol) was dissolved in DMF (3.5 mL). To this solution was added [2-chloro-5-(trifluoromethyl)phenyl]-boronic acid (370 mg, 1.6 mmol), palladium(II)acetate (7 mg), triphenylphosphine (18 mg) and triethylamine (0.46 mL). The whole mixture was heated with stirring at 100° C. for 20 h, cooled to room temperature and partitioned between dichloromethane and a mixture of water and concentrated ammonium hydroxide solution (water/ammonia 4:1 v/v). Organic phases were pooled, dried with MgSO4 and the solvent was evaporated. The residue was purified by column chromatography on silica (n-heptane/ethyl acetate 6:1) to yield 0.27 g of the title compound as a light yellow oil, MS (ISP) 400.4 (M+H)+.

Workup

  1. temperatureThe whole mixture was heated
  2. temperaturecooled to room temperature
  3. custompartitioned between dichloromethane
  4. additiona mixture of water and concentrated ammonium hydroxide solution (water/ammonia 4:1 v/v)
  5. dry with materialdried with MgSO4
  6. customthe solvent was evaporated
  7. customThe residue was purified by column chromatography on silica (n-heptane/ethyl acetate 6:1)

Sources & evidence

ORD record
ord-8864d714172d4e75aa8ca8661ecfd70a
Source dataset
uspto-grants-2007_06
Patent number
US07229999B2

Reaction notes

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