Potassium Carbonate → Methyl 5'-(difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-carboxylate

HRID 1662441Notes

Reaction equation

HRID 1662441 reaction equation
[CH3:1][C:2]1([CH3:25])[C:6]([C:7]2[CH:8]=[C:9]([CH:14]=[CH:15][C:16]=2OS(C(F)(F)F)(=O)=O)[C:10]([O:12][CH3:13])=[O:11])=[CH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[F:32][CH:33]([F:50])[C:34]1[CH:35]=[CH:36][C:37]([F:49])=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:39]=1>CN(C=O)C.O.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>[F:32][CH:33]([F:50])[C:34]1[CH:35]=[CH:36][C:37]([F:49])=[C:38]([C:16]2[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][C:7]=2[C:6]2[C:2]([CH3:25])([CH3:1])[CH2:3][CH2:4][CH:5]=2)[CH:39]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 57467618Methyl 3-(5,5-dimethylcyclopent-1-enyl)-4-(trifluoromethylsulfonyloxy)benzoateHCID 574676372-(5-(Difluoromethyl)-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 57705519Methyl 5'-(difluoromethyl)-2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-1,1'-biphenyl-4-carboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 66.6I (1.1209 g, 2.962 mmol) in dry DMF (10 mL) at 23° C. was added potassium carbonate (1.2262 g, 8.872 mmol) and then tetrakis(triphenylphosphine)palladium (0.3408 g, 0.2949 mmol). The mixture was purged with argon and placed under vacuum and the purging and vacuum process repeated three times. Before heating, 66.50A (1.6019 g, 5.888 mmol) was added via syringe and then the mixture was heated to 90° C. After 19 hours, LC-MS showed that the reaction was complete. The mixture was cooled to room temperature and then diluted with water. After extracting three times with EtOAc, the mixture was concentrated in vacuo and then purified on silica gel (0%-10% EtOAc/hexane) to afford 66.50B as a clear oil (994.4 mg, 90% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.00 (1H, dd, J=8.0, 1.8 Hz), 7.94 (1H, d, J=1.6 Hz), 7.50 (3H, m), 7.16 (1H, t, J=9.0 Hz), 6.63 (1H, t), 5.53 (1H, s), 3.96 (3H, s), 2.25 (2H, td, J=7.0, 2.3 Hz), 1.65 (2H, t, J=7.0 Hz), 0.85 (6H, s).

Workup

  1. customThe mixture was purged with argon
  2. temperatureBefore heating
  3. temperatureThe mixture was cooled to room temperature
  4. extractionAfter extracting three times with EtOAc
  5. concentrationthe mixture was concentrated in vacuo
  6. custompurified on silica gel (0%-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-e78118e03e6047d381fd8400c8b34f6e
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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