Sodium Hydroxide → HCID 68899827, compound

HRID 735322Notes

Reaction equation

HRID 735322 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][OH:22])(=[O:14])=[O:13])[CH:6]=[CH:5]2.[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][OH:22])(=[O:14])=[O:13])[CH:6]=[CH:5]2

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 27343342,4-Difluorophenylboronic acidHCID 27349382-(Dicyclohexylphosphino)-2'-methylbiphenylHCID 68902440HCID 68902440, compound

Product 1

HCID 68899827HCID 68899827, compoundYield 17.1%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of {2-[(6-chloroquinolin-2-yl)sulfonyl]phenyl}methanol (Step 2, 157 mg, 0.47 mmol), 2,4-difluorobenzeneboronic acid (173 mg, 1.09 mmol), palladium acetate (6 mg, 0.023 mmol), 2-dicyclohexylphosphino-2′-methylbiphenyl (18 mg, 0.05 mmol) and potassium phosphate (313 mg, 1.47 mmol) was degassed. Toluene (2 mL) was added and the mixture degassed again then heated to 90° C. under nitrogen for 1 hour. The cooled reaction mixture was poured into 1M sodium hydroxide solution and extracted with ethyl acetate (x2). The combined organic layers were washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash column chromatography on silica, eluting with 5-10% ethyl acetate/isohexane, followed by recrystallisation from ethyl acetate/isohexane to give the title compound (33 mg, 17%). 1H NMR (500 MHz, CDCl3) δ 8.46 (1H, d, J=8.5 Hz), 8.27 (1H, d, J=8.5 Hz), 8.20 (1H, d, J=7.9 Hz), 8.16 (1H, d, J=8.9 Hz), 8.02 (1H, s), 7.94 (1H, d, J=8.8 Hz), 7.65-7.59 (2H, m), 7.53-7.47 (2H, m), 7.04-6.96 (2H, m), 5.12 (2H, d, J=7.0 Hz), 4.18 (1H, t, J=7.1 Hz); m/z (ES+) 412 [MH+].

Workup

  1. customwas degassed
  2. additionToluene (2 mL) was added
  3. customthe mixture degassed again
  4. customThe cooled reaction mixture
  5. extractionextracted with ethyl acetate (x2)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue was purified by flash column chromatography on silica
  10. washeluting with 5-10% ethyl acetate/isohexane
  11. customfollowed by recrystallisation from ethyl acetate/isohexane

Sources & evidence

ORD record
ord-959a7be071f84190a2fafb30167d56a7
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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