Dichloromethane → 4-(4'-Difluoromethoxy-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acid methyl ester

HRID 490388Notes

Reaction equation

HRID 490388 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]([CH3:27])=[C:8]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[CH:9]=1)=[O:4].[F:28][CH:29]([F:38])[O:30][C:31]1[CH:36]=[CH:35][C:34](I)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[O:6][C:7]([CH3:27])=[C:8]([CH2:10][O:11][C:12]2[CH:13]=[CH:14][C:15]([C:34]3[CH:35]=[CH:36][C:31]([O:30][CH:29]([F:38])[F:28])=[CH:32][CH:33]=3)=[CH:16][CH:17]=2)[CH:9]=1)=[O:4]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 10796Cesium carbonateHCID 27370081-(Difluoromethoxy)-4-iodobenzene2×HCID 588241625-Methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-furan-2-carboxylic acid methyl ester

Product 1

HCID 588241674-(4'-Difluoromethoxy-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acid methyl esterYield 57.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A degassed mixture of 5-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxymethyl]-furan-2-carboxylic acid methyl ester (119) (200 mg, 0.54 mmoles), 4-difluoromethoxy-1-iodo-benzene (175 mg, 0.65 mmoles), 2M aqueous cesium carbonate (0.81 ml) and), [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (20 mg) in 1,4-dioxan (10 ml), under an argon atmosphere was heated at 80° C. for 20 h. Further quantities of 4-difluoromethoxy-1-iodo-benzene (87.5 mg, 0.0.27 mmoles) and [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (10 mg) were added and heating at 80° C. was continued for 4 hours. After cooling, the mixture was concentrated. The residue was dissolved in dichloromethane and washed with water and brine, and dried. The solvent was evaporated and the residue was purified by flash chromatography using petrol (40-60°)/diethyl ether 9:1 v/v as eluent to afford compound 128 (120 mg) as a wax. LC/MS System A; Rt=4.14 mins.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washwashed with water and brine
  5. customdried
  6. customThe solvent was evaporated
  7. customthe residue was purified by flash chromatography
  8. custompetrol (40-60°)/diethyl ether 9:1 v/v

Sources & evidence

ORD record
ord-79beb47e9f2d41e7b09db009b8e98296
Source dataset
uspto-grants-2009_05
Patent number
US07528157B2

Reaction notes

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