Isopropanol → HCID 68830000, compound

HRID 2100376Notes

Reaction equation

HRID 2100376 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.[OH-:18].[Na+].[CH:20]([OH:23])([CH3:22])[CH3:21]>CO.[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:21]3[CH:11]=[CH:12][C:7]([C:5]([OH:6])=[O:18])=[CH:22][C:20]=3[O:23][CH2:2][CH2:1][CH3:3])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 14798Sodium Hydroxide2×HCID 21914527(5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid

Product 1

HCID 68830000HCID 68830000, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

Intermediate 10 (75 mg), {5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}boronic acid (79 mg) and tetrakis(triphenylphosphine) palladium (0) (10 mg) were combined in isopropanol (2.5 ml). Aqueous sodium hydroxide solution (1M, 0.81 ml) was added and the reaction stirred under nitrogen at 90° C. for 5 hours. The solvent was evaporated in vacuo and the residue partitioned between ethyl acetate/chloroform (1:1, 5 ml) and water (5 ml) and the aqueous extracted with ethyl acetate/chloroform (1:1, 2×5 ml). The organic layers were combined, dried using a hydrophobic filter, and evaporated to leave a yellow gel. The residue was stirred in methanol (1) and aqueous sodium hydroxide solution (2M, 1 ml) under nitrogen at 20° C. for 16 hours. The solvent was evaporated and the residue partitioned between ethyl acetate/chloroform (1:1, 2×10 ml) and water (10 ml). The aqueous layer was acidified to pH1 using concentrated hydrochloric acid, and extracted with ethyl acetate/chloroform (1:1). The organic layers were combined, dried using a hydrophobic filter, and evaporated to leave a white solid. This material was applied to an SPE cartridge (1 g aminopropyl), the cartridge washed with methanol/chloroform (1:9), and the product eluted with acetic acid/rethanollchloroform (1:1:8); to give, after evaporation of the solvents under vacuum, 5′-[(cyclopropylamino)carbonyl]-3′-fluoro-2′-methyl-2-(propyloxy)-4-biphenylcarboxylic acid as a colourless gel (47 mg).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between ethyl acetate/chloroform (1:1, 5 ml) and water (5 ml)
  3. extractionthe aqueous extracted with ethyl acetate/chloroform (1:1, 2×5 ml)
  4. customdried
  5. customevaporated
  6. customto leave a yellow gel
  7. customThe solvent was evaporated
  8. customthe residue partitioned between ethyl acetate/chloroform (1:1, 2×10 ml) and water (10 ml)
  9. extractionextracted with ethyl acetate/chloroform (1:1)
  10. customdried
  11. customevaporated
  12. customto leave a white solid
  13. washthe cartridge washed with methanol/chloroform (1:9)
  14. washthe product eluted with acetic acid/rethanollchloroform (1:1:8)
  15. customto give
  16. customafter evaporation of the solvents under vacuum, 5′-[(cyclopropylamino)carbonyl]-3′-fluoro-2′-methyl-2-(propyloxy)-4-biphenylcarboxylic acid as a colourless gel (47 mg)

Sources & evidence

ORD record
ord-43297e20671c4ed493bf1e28cc679bfd
Source dataset
uspto-grants-2009_08
Patent number
US07572790B2

Reaction notes

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