Potassium Phosphate, Tribasic → Methyl 3'-((difluoromethyl)oxy)-2-(2,2-dimethylcyclopentyl)-1,1'-biphenyl-4-carboxylate

HRID 1662378Notes

Reaction equation

HRID 1662378 reaction equation
[CH3:1][C:2]1([CH3:25])[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][C:16]=1OS(C(F)(F)F)(=O)=O)[C:10]([O:12][CH3:13])=[O:11].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[F:63][CH:64]([F:81])[O:65][C:66]1[CH:67]=[C:68](B2OC(C)(C)C(C)(C)O2)[CH:69]=[CH:70][CH:71]=1>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:63][CH:64]([F:81])[O:65][C:66]1[CH:71]=[C:70]([C:16]2[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][C:7]=2[CH:3]2[CH2:4][CH2:5][CH2:6][C:2]2([CH3:25])[CH3:1])[CH:69]=[CH:68][CH:67]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574676152-(3-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 57706600Methyl 3-(2,2-dimethylcyclopentyl)-4-(trifluoromethylsulfonyloxy)benzoate

Product 1

HCID 57706023Methyl 3'-((difluoromethyl)oxy)-2-(2,2-dimethylcyclopentyl)-1,1'-biphenyl-4-carboxylateYield 65.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A stirred mixture of 66.11F (0.48 g, 1.26 mmol), ground S-Phos (104.8 mg, 0.255 mmol), palladium acetate (29.1 mg, 0.130 mmol), and potassium phosphate tribasic (0.6727 g, 3.17 mmol) in dry DMF (5.0 mL) was purged with argon and placed under vacuum (repeated three times). Before heating, 66.11B (0.512 g, 1.89 mmol) was added via syringe, and then the mixture was heated to 75° C. After 16 hours, the reaction was cooled to room temperature, diluted with water and extracted three times with EtOAc. The combined organic layers were washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified on silica gel (0-20% EtOAc in hexanes) to yield 66.11G as a colorless oil (308.9 mg, 65%). 1H NMR (500 MHz, CDCl3) δ ppm 8.11 (1H, d, J=1.7 Hz), 7.90 (1H, dd, J=7.9, 1.8 Hz), 7.44 (1H, m), 7.28 (1H, m), 7.16 (2H, m), 7.07 (1H, s), 6.57 (1H, t, J=75 Hz), 3.97 (3H, s), 3.10 (1H, t, J=9.4 Hz), 2.13 (2H, m), 1.90 (1H, m), 1.73 (1H, m), 1.61 (1H, m), 1.38 (1H, ddd, J=12.6, 9.4, 7.6 Hz), 0.75 (3H, s), 0.58 (3H, s).

Workup

  1. customwas purged with argon
  2. temperatureBefore heating
  3. temperaturethe reaction was cooled to room temperature
  4. extractionextracted three times with EtOAc
  5. washThe combined organic layers were washed twice with brine
  6. dry with materialAfter drying over anhydrous sodium sulfate and filtration
  7. customthe organic solvent was removed under reduced pressure
  8. customThe residue was purified on silica gel (0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-354e677e080e4b54a411cb4575bd86f1
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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