Sodium Sulfite → 4,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carboxylic acid

HRID 1054636Notes

Reaction equation

HRID 1054636 reaction equation
[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([CH3:21])([CH3:20])[CH2:18][OH:19])=[CH:13][CH:12]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([CH:23]=[O:24])=[CH:5][NH:6]2.Cl([O-])=[O:26].[Na+].P([O-])(O)(O)=O.[Na+].S([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C(O)(C)(C)C.CC(=CC)C.O>[F:1][C:2]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([CH3:21])([CH3:20])[CH2:18][OH:19])=[CH:15][CH:16]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([C:23]([OH:26])=[O:24])=[CH:5][NH:6]2

Participants

9

Reactant 4

HCID 24437Sodium SulfiteHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 866986404,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carbaldehyde

Product 1

HCID 717658004,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carboxylic acidYield 42%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 105532-Methyl-2-buteneSolvent

Procedure

To a solution of 4,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carbaldehyde (40 mg, 0.122 mmol) in acetonitrile (2.3 mL), t-butanol (2.3 mL) and 2-methyl-2-butene (1.5 mL) was added a solution of sodium chlorite (164 mg, 2.43 mmol) and sodium dihydrogen phosphate (335 mg, 2.43 mmol) in water (2.3 mL) at 0° C. The reaction mixture was stirred at room temperature for 18 h. The reaction was quenched with a solution of sodium sulfite (337 mg, 2.68 mmol) in water (5.0 mL), and extracted with ethyl acetate (10 mL×3). The organic layers were washed with brine (10 mL) and dried over sodium sulfate, filtered and concentrated to give a crude residue, which was purified by reverse phase HPLC to give the title compound (14.6 mg, 42%) as a white solid.

Workup

  1. extractionextracted with ethyl acetate (10 mL×3)
  2. washThe organic layers were washed with brine (10 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude residue, which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e9586a9a441a4e188814a3e26aff13f1
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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