Water → methyl 3-chloro-2-hydroxy-5-[4-(1H-pyrazol-1-yl)benzyl]-4-(trifluoromethyl)benzoate

HRID 629361

Reaction equation

HRID 629361 reaction equation
[Cl:1][C:2]1[C:3]([OH:25])=[C:4]([CH:9]=[C:10](B2OC(C)(C)C(C)(C)O2)[C:11]=1[C:12]([F:15])([F:14])[F:13])[C:5]([O:7][CH3:8])=[O:6].Cl[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH:38]=[CH:37][CH:36]=[N:35]2)=[CH:30][CH:29]=1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([OH:25])=[C:4]([CH:9]=[C:10]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([N:34]3[CH:38]=[CH:37][CH:36]=[N:35]3)=[CH:32][CH:33]=2)[C:11]=1[C:12]([F:13])([F:14])[F:15])[C:5]([O:7][CH3:8])=[O:6].[Cl:1][C:2]1[C:3]([OH:25])=[C:4]([CH:9]=[C:10]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([N:34]3[CH:38]=[CH:37][CH:36]=[N:35]3)=[CH:32][CH:33]=2)[C:11]=1[C:12]([F:13])([F:14])[F:15])[C:5]([OH:7])=[O:6]

Participants

9

Reactant 4

HCID 962WaterHCID 71308871-[4-(chloromethyl)phenyl]-1H-pyrazoleHCID 18407952Tripotassium phosphate trihydrateHCID 131735369Methyl 3-chloro-2-hydroxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzoate

Product 2

HCID 118468170methyl 3-chloro-2-hydroxy-5-[4-(1H-pyrazol-1-yl)benzyl]-4-(trifluoromethyl)benzoateHCID 1184684273-chloro-2-hydroxy-5-[4-(1H-pyrazol-1-yl)benzyl]-4-(trifluoromethyl)benzoic acid

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 3-chloro-2-hydroxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)benzoate (1.50 g) in 1,4-dioxane (30.0 mL) were added 1-(4-(chloromethyl)phenyl)-1H-pyrazole (0.76 g), tetrakis(triphenylphosphine)palladium(0) (0.23 g) and tripotassium phosphate trihydrate (2.10 g), and the mixture was stirred at 90° C. for 16 hr under nitrogen atmosphere. The reaction mixture was allowed to be cooled to room temperature, water and ethyl acetate were added thereto, and the mixture was partitioned. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by flash silica gel column chromatography (ethyl acetate/petroleum ether) to give methyl 3-chloro-2-hydroxy-5-[4-(1H-pyrazol-1-yl)benzyl]-4-(trifluoromethyl)benzoate (0.12 g) and 3-chloro-2-hydroxy-5-[4-(1H-pyrazol-1-yl)benzyl]-4-(trifluoromethyl)benzoic acid (0.70 g).

Workup

  1. temperatureto be cooled to room temperature
  2. customthe mixture was partitioned
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by flash silica gel column chromatography (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-32eb98c2ab494121bd3966240aee84c0
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Linked notes

Loading…