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

HRID 1662525Notes

Reaction equation

HRID 1662525 reaction equation
C1([C@H](C2C=CC=C([O:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20](C4C=C(OC)C=CC=4F)=[C:19]([C@@H:32]4[CH2:36][CH2:35][CH2:34][C:33]4([CH3:38])[CH3:37])[CH:18]=3)C=2)CC(O)=O)CC1.[C:39](=O)([O-])[O-:40].[K+].[K+].[F:45][CH:46]([F:63])[C:47]1[CH:48]=[CH:49][C:50]([F:62])=[C:51](B2OC(C)(C)C(C)(C)O2)[CH:52]=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:63][CH:46]([F:45])[C:47]1[CH:48]=[CH:49][C:50]([F:62])=[C:51]([C:20]2[CH:21]=[CH:22][C:17]([C:16]([O:40][CH3:39])=[O:15])=[CH:18][C:19]=2[C:32]2[C:33]([CH3:38])([CH3:37])[CH2:34][CH2:35][CH:36]=2)[CH:52]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 574676372-(5-(Difluoromethyl)-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 57706097(3r)-3-Cyclopropyl-3-(3-(((2-((1r)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoic acid

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 66.6 I (1.12 g, 2.96 mmol) in DMF (10 mL) at 23° C. was added potassium carbonate (1.23 g, 8.87 mmol) followed by tetrakis(triphenylphosphine)palladium (0.34 g, 0.29 mmol). The mixture was purged three times with argon and placed under vacuum three times. Before heating, 83.3A (1.60 g, 5.89 mmol) was added via syringe, and then the mixture was heated to 90° C. After 19 hours, 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 give 83.3B as a clear oil (0.99, 90%). 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 three times 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-4bdc99621308408ba7b55af7d119adb4
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

Loading…