Isopropanol → HCID 68829089, compound

HRID 2100381Notes

Reaction equation

HRID 2100381 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[C:9]([F:17])[C:10]([CH3:16])=[C:11](B(O)O)[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.[C:18](=[O:21])([O-])[OH:19].[Na+].[CH:23]([OH:26])([CH3:25])[CH3:24]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[C:9]([F:17])[C:10]([CH3:16])=[C:11]([C:24]3[CH:3]=[CH:1][C:2]([C:18]([OH:19])=[O:21])=[CH:25][C:23]=3[O:26][CH2:11][CH2:12][CH2:7][CH2:5][OH:6])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 516892Sodium BicarbonateHCID 21914527(5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid

Product 1

HCID 68829089HCID 68829089, compound

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

Intermediate 23 (318 mg), {5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}boronic acid (252 mg) and tetrakis(triphenylphosphine) palladium (0) (45 mg) were combined in isopropanol and aqueous sodium hydrogen carbonate solution (1M, 2.7 ml) added. The reaction was stirred under nitrogen at 90° C. for 6 hours. The solvent was evaporated in vacuo and the residue partitioned between ethyl acetate/chloroform (1:1) and water. The organic phase was dried using a hydrophobic filter, the solvent evaporated under vacuum. The residue was dissolved in methanol (10 ml), aqueous sodium hydroxide solution (2M, 10 ml) added and the reaction stirred at 20° C. for 18 hours. The solvents were evaporated and residue partitioned between ethyl acetate/chloroform (1:1) and water. The aqueous layer was acidified to pH1 using concentrated hydrochloric acid and extracted with ethyl acetate/chloroform (1:1). The organic phase was dried using a hydrophobic filter and evaporated, and the residue purified using SPE (5 g, Si), eluting with a methanol/chloroform gradient (1-10%). The solvents were evaporated from the product fraction in vacuo to give 5′-[(cyclopropylamino)carbonyl]-3′-fluoro-2-[(4-hydroxybutyl)oxy]-2′-methyl-4-biphenylcarboxylic acid as a cream solid (140 mg).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between ethyl acetate/chloroform (1:1) and water
  3. customThe organic phase was dried
  4. customthe solvent evaporated under vacuum
  5. dissolutionThe residue was dissolved in methanol (10 ml)
  6. additionaqueous sodium hydroxide solution (2M, 10 ml) added
  7. stirringthe reaction stirred at 20° C. for 18 hours
  8. customThe solvents were evaporated
  9. customresidue partitioned between ethyl acetate/chloroform (1:1) and water
  10. extractionextracted with ethyl acetate/chloroform (1:1)
  11. customThe organic phase was dried
  12. filtrationa hydrophobic filter
  13. customevaporated
  14. customthe residue purified
  15. washeluting with a methanol/chloroform gradient (1-10%)
  16. customThe solvents were evaporated from the product fraction in vacuo

Sources & evidence

ORD record
ord-e145da9c76464e7383fbe63ae750e1b5
Source dataset
uspto-grants-2009_08
Patent number
US07572790B2

Reaction notes

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