Dimethylformamide → 4-(4'-Acetyl-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acid

HRID 2266791Notes

Reaction equation

HRID 2266791 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].[C:20]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)(=[O:22])[CH3:21].CN(C)C=O.C([O-])(=O)C.[K+]>ClCCl>[C:20]([C:23]1[CH:28]=[CH:27][C:26]([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:24]=1)(=[O:22])[CH3:21]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 517044Potassium AcetateHCID 37021224-Acetylphenylboronic acidHCID 588241574-(4-Iodo-phenoxymethyl)-5-methyl-furan-2-carboxylic acid methyl ester

Product 1

HCID 184445574-(4'-Acetyl-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A stirred mixture of 4-(4-iodo-phenoxymethyl)-5-methyl-furan-2-carboxylic acid methyl ester (20) (0.26 g), 4-acetylphenylboronic acid (0.15° g), N,N-dimethylformamide (30 mL), potassium acetate (0.26 g) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(11), complex with dichloromethane (1:1) (40 mg) was heated at 90° C. over night. The reaction mixture was concentrated in vacuo, dissolved in ethyl acetate (30 mL) and washed successively with water (30 mL), brine (30 mL), dried and 3 concentrated in vacuo. The residue was dissolved in a mixture of tetrahydrofuran/methanol (2:1 by volume) (30 mL) and 1.0 M aqueous lithium hydroxide solution (6.78 mL) and stirred for 16 hours. The reaction mixture was acidified to pH 2 using 0.1 M hydrochloric acid and extracted with ethyl acetate (3×25 mL). The extract was dried, concentrated in vacuo and the residue purified by HPLC to give compound 21 as a white solid (50 mg). LC/MS System C: Rt=4.18 mins, m/z (ES−)=349 (M− for C21H18O5).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutiondissolved in ethyl acetate (30 mL)
  3. washwashed successively with water (30 mL), brine (30 mL)
  4. customdried
  5. concentration3 concentrated in vacuo
  6. dissolutionThe residue was dissolved in a mixture of tetrahydrofuran/methanol (2:1 by volume) (30 mL) and 1.0 M aqueous lithium hydroxide solution (6.78 mL)
  7. extractionextracted with ethyl acetate (3×25 mL)
  8. customThe extract was dried
  9. concentrationconcentrated in vacuo
  10. customthe residue purified by HPLC

Sources & evidence

ORD record
ord-7b9f43ade6bc429ca5b9c43fadfbe346
Source dataset
uspto-grants-2010_12
Patent number
US07858644B2

Reaction notes

Loading…