Water → 2,4-difluoro-3-[hydroxy-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenol

HRID 1098389Notes

Reaction equation

HRID 1098389 reaction equation
[F:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([F:10])[CH:5]=[CH:4][C:3]=1[O:11]C(=O)OC(C)(C)C.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]2[CH:26]=[C:27]3[CH:33]=[CH:32][NH:31][C:28]3=[N:29][CH:30]=2)[CH:20]=1.[OH-].[K+].O>CO>[F:1][C:2]1[C:7]([CH:8]([OH:9])[C:33]2[C:27]3[C:28](=[N:29][CH:30]=[C:25]([C:21]4[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=4)[CH:26]=3)[NH:31][CH:32]=2)=[C:6]([F:10])[CH:5]=[CH:4][C:3]=1[OH:11]

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 513585515-(Pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridineHCID 58086191Carbonic acid tert-butyl ester 2,4-difluoro-3-formyl-phenyl ester

Product 1

HCID 580862122,4-difluoro-3-[hydroxy-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To carbonic acid tert-butyl ester 2,4-difluoro-3-formyl-phenyl ester (39, 0.405 g, 15.7 mmol) in methanol (36 mL), under an atmosphere of nitrogen, was added 5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine (89, 288.0 mg, 14.8 mmol, prepared as described in Example 17) and potassium hydroxide (145.0 mg, 25.9 mmol). The reaction was stirred at room temperature overnight. Then, the reaction was poured into water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated. The mixture was purified by silica gel column chromatography eluting with 4% methanol in methylene chloride to provide two separate compounds, a colorless oil (P-0009, 0.23 g, 44.1%, MS (ESI) [M+H+]+=354.1), and a colorless oil (P-0042, 0.050 g, 9.2%, MS (ESI) [M+H+]+=367.1).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe mixture was purified by silica gel column chromatography
  6. washeluting with 4% methanol in methylene chloride
  7. customto provide two
  8. customseparate compounds

Sources & evidence

ORD record
ord-86672f81f0544118b94dbcd90f06148e
Source dataset
uspto-grants-2012_03
Patent number
US08143271B2

Reaction notes

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