Sodium Hydroxide → HCID 86692498, compound

HRID 1748550Notes

Reaction equation

HRID 1748550 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:12]2[C:17](Cl)=[CH:16][C:15]([C:19]([F:22])([F:21])[F:20])=[CH:14][N:13]=2)[C:10]=1[CH3:11])=[O:5])C.[CH3:23]B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO.O1CCCC1.O>[CH3:11][C:10]1[N:9]([C:12]2[C:17]([CH3:23])=[CH:16][C:15]([C:19]([F:20])([F:21])[F:22])=[CH:14][N:13]=2)[N:8]=[CH:7][C:6]=1[C:4]([OH:3])=[O:5]

Participants

11

Reactant 5

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 139377Methylboronic AcidHCID 1475765HCID 1475765, compoundHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 86692498HCID 86692498, compoundYield 27.2%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (3 g) in Reference Example 123 (2), methylboronic acid (807 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (185 mg), palladium acetate (101 mg) and tripotassium phosphate (5.72 g) in 1,4-dioxane (20 ml) was stirred at 120° C. After completion of the reaction, the mixture was allowed to cool to room temperature, 4 N aqueous solution of sodium hydroxide (30 ml), water (30 ml), tetrahydrofuran (10 ml) and methanol (20 ml) were added thereto, and stirred at room temperature overnight. The organic solvent was evaporated in vacuo, then water and diethyl ether were added thereto, and the aqueous layer was separated. To the aqueous layer was added concentrated hydrochloric acid under ice-cooling to adjust the layer to pH 5, and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The obtained residue was purified with silica gel chromatography (chloroform/methanol) to give the titled compound (697 mg) as a brown solid. MS (ESI) m/z: 286 (M+H)+.

Workup

  1. customAfter completion of the reaction
  2. temperatureto cool to room temperature
  3. stirringstirred at room temperature overnight
  4. customThe organic solvent was evaporated in vacuo
  5. additionwater and diethyl ether were added
  6. customthe aqueous layer was separated
  7. additionTo the aqueous layer was added concentrated hydrochloric acid under ice-
  8. temperaturecooling
  9. extractionextracted with chloroform
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. customthe solvent was evaporated in vacuo
  12. customThe obtained residue was purified with silica gel chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-d832d3765da441b38f1442465cca72d5
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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