Dimethylformamide → 4-(3',4'-Dimethoxy-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acid

HRID 490365Notes

Reaction equation

HRID 490365 reaction equation
C[O:2][C:3]([C:5]1[O:6][C:7]([CH3:19])=[C:8]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][CH:13]=2)[CH:9]=1)=[O:4].[CH3:20][O:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29].CN(C)C=O.C([O-])(=O)C.[K+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH3:20][O:21][C:22]1[CH:23]=[C:24]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH2:10][C:8]3[CH:9]=[C:5]([C:3]([OH:2])=[O:4])[O:6][C:7]=3[CH3:19])=[CH:13][CH:14]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 517044Potassium AcetateHCID 27347023,4-Dimethoxyphenylboronic acidHCID 588241574-(4-Iodo-phenoxymethyl)-5-methyl-furan-2-carboxylic acid methyl ester

Product 1

HCID 184445504-(3',4'-Dimethoxy-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acidYield 60.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred mixture of 4-(4-iodo-phenoxymethyl)-5-methyl-furan-2-carboxylic acid methyl ester (20) (0.025 g, 0.067 mmoles), (3,4-dimethoxyphenyl)-boronic acid (0.017 g, 0.093 mmoles), N,N-dimethylformamide (3 mL), potassium acetate (0.026 g) and [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (4 mg) was stirred at room temperature under an argon atmosphere for 24 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The extracts were washed with water, dried and concentrated in vacuo. The residue was dissolved in a mixture of tetrahydrofuran/methanol (2:1 by volume) (2.5 mL) and 1.0 M aqueous lithium hydroxide solution (0.5 mL), and stirred for 16 hours. The reaction mixture was acidified to pH=6 using 1M hydrochloric acid and extracted with ethyl acetate (3×25 mL). The extracts were dried, concentrated in vacuo and the residue purified by HPLC (gradient: 30% acetonitrile/70% water containing 0.1% trifluoroacetic acid to 70% acetonitrile/30% water at a rate of 1%/min) to give compound 96 as a solid (15 mg). LC/MS System B; Rt=1.65 mins, m/z (ES−)=367 (M−H for C21H20O6).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extracts were washed with water
  3. customdried
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in a mixture of tetrahydrofuran/methanol (2:1 by volume) (2.5 mL) and 1.0 M aqueous lithium hydroxide solution (0.5 mL)
  6. stirringstirred for 16 hours
  7. extractionextracted with ethyl acetate (3×25 mL)
  8. customThe extracts were dried
  9. concentrationconcentrated in vacuo
  10. customthe residue purified by HPLC (gradient

Sources & evidence

ORD record
ord-a9060a441cc5449b9778fb1c0f1cf445
Source dataset
uspto-grants-2009_05
Patent number
US07528157B2

Reaction notes

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