Water → 5-(4-Chloro-phenyl)-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid

HRID 598248Notes

Reaction equation

HRID 598248 reaction equation
C([O:3][C:4](=[O:22])[C:5]1[CH:10]=[C:9](Br)[C:8]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[N:7][C:6]=1[C:18]([F:21])([F:20])[F:19])C.[Cl:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.O.[OH-].[Li+]>C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(C)C=CC=CC=1>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:9]2[C:8]([O:12][CH2:13][C:14]([F:15])([F:16])[F:17])=[N:7][C:6]([C:18]([F:19])([F:20])[F:21])=[C:5]([CH:10]=2)[C:4]([OH:22])=[O:3])=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 962Water3×HCID 3939Lithium Hydroxide2×HCID 742994-Chlorophenylboronic acidHCID 866347975-Bromo-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid ethyl ester

Product 1

HCID 866348055-(4-Chloro-phenyl)-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

5-Bromo-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid ethyl ester (2 g, 5.05 mmol) was dissolved in ethanol (30 ml). To this solution was added with stirring [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) CH2Cl2 (41.2 mg, 0.05 mmol), 4-chlorophenylboronic acid (828.8 mg, 5.3 mmol), water (4.8 ml) and lithium hydroxide (246.7 mg, 10.1 mmol). This mixture was heated to 70° C. for 2.5 h and cooled to room temperature. Water (12 mL) and lithium hydroxide (370.0 mg, 15.1 mmol) was added and stirred at 70° C. for 0.5 h. The reaction mixture was cooled to room temperature, treated with water (40 ml) and toluene (40 ml) and extracted. The phases were separated, the organic phase extracted with water (30 ml). The combined water phase was acidified with HCl 2N and extracted with ethylacetate. Organic phases were pooled, dried with Na2SO4 and the volatiles removed in vacuo. The residue was dissolved in ethanol (6 ml) and treated with water (12 ml) to give after crystallization the title compound (1.82 g) as light brown crystals; MS (ISN) 398.0 (M−H)−.

Workup

  1. temperaturecooled to room temperature
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted
  4. customThe phases were separated
  5. extractionthe organic phase extracted with water (30 ml)
  6. extractionextracted with ethylacetate
  7. dry with materialdried with Na2SO4
  8. customthe volatiles removed in vacuo
  9. dissolutionThe residue was dissolved in ethanol (6 ml)
  10. additiontreated with water (12 ml)
  11. customto give
  12. customafter crystallization the title compound (1.82 g) as light brown crystals

Sources & evidence

ORD record
ord-77078c99733a4fe9b2e7c729141e0d24
Source dataset
uspto-grants-2011_03
Patent number
US07897621B2

Reaction notes

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