1,2-Dimethoxyethane → 2'-fluoro-5-(2-isopropyl-2H-pyrazol-3-yl)-4'-methyl-biphenyl-3-carboxylic acid methyl ester

HRID 2091819Notes

Reaction equation

HRID 2091819 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=2[F:19])[CH:8]=[C:9](I)[CH:10]=1)=[O:4].[CH:20]([N:23]1[C:27](B(O)O)=[CH:26][CH:25]=[N:24]1)([CH3:22])[CH3:21].CC([O-])=O.[K+].COCCOC>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.O>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=2[F:19])[CH:8]=[C:9]([C:27]2[N:23]([CH:20]([CH3:22])[CH3:21])[N:24]=[CH:25][CH:26]=2)[CH:10]=1)=[O:4]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 517044Potassium AcetateHCID 23139440(1-Isopropyl-1H-pyrazol-5-yl)boronic acidHCID 594325542'-Fluoro-5-iodo-4'-methyl-biphenyl-3-carboxylic acid methyl ester

Product 1

HCID 577706482'-fluoro-5-(2-isopropyl-2H-pyrazol-3-yl)-4'-methyl-biphenyl-3-carboxylic acid methyl esterYield 55.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

To a microwave vessel was added 2′-fluoro-5-iodo-4′-methyl-biphenyl-3-carboxylic acid methyl ester (1.91 g, 5.4 mmol), 2-isopropyl-2H-pyrazole-3-boronic acid (1.08 g, 7.02 mmol), KOAc (1.59 g, 16.2 mmol), Pd(PPh3)4 (0.187 g, 0.16 mmol), dimethylglycol (15 mL) and water (3 mL). The mixture was flushed with N2 before submitting to microwave heating at 130° C. for 1 hour. After cooling down to room temperature, the reaction mixture was extracted with EtOAc and the combined organic layers were washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column to afford 2′-fluoro-5-(2-isopropyl-2H-pyrazol-3-yl)-4′-methyl-biphenyl-3-carboxylic acid methyl ester as a viscous oil (1.0 g, 55.2%).

Workup

  1. customThe mixture was flushed with N2
  2. temperatureAfter cooling down to room temperature
  3. extractionthe reaction mixture was extracted with EtOAc
  4. washthe combined organic layers were washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column

Sources & evidence

ORD record
ord-f1f047b38d5a4230abcccf13a89d554b
Source dataset
uspto-grants-2013_05
Patent number
US08440673B2

Reaction notes

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