Tetrahydrofuran → HCID 178505888, compound

HRID 230129Notes

Reaction equation

HRID 230129 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].CC(C)([O-])C.[K+].C1COCC1.[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[C:36]2[C:31](=[N:32][C:33](S(C)(=O)=O)=[N:34][CH:35]=2)[NH:30][N:29]=1>C(OCC)(=O)C.[Cl-].[NH4+].O>[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[C:36]2[C:31](=[N:32][C:33]([O:9][C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[N:34][CH:35]=2)[NH:30][N:29]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 1230512,4-DifluorophenolHCID 23665647Potassium tert-butoxideHCID 178504839HCID 178504839, compound

Product 1

HCID 178505888HCID 178505888, compoundYield 158.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a neat sample of 2,4-difluorophenol (Aldrich) (379 mg, 3 eq) in a Microwave Reactor Vessel, at 0° C. was added dropwise a 1.0 M potassium tert-butoxide solution in THF (2.9 mL, 3.05 eq). The mixture was stirred 5 minutes and then warmed to room temperature. Solid 3-(2-chlorophenyl)-6-methylsulfonyl-1H-pyrazolo[3,4-d]pyrimidine (300 mg, 0.971 mmol) was added and the reaction mixture was placed in a Microwave Reactor and heated at 120° C. for 15 minutes. The reaction mixture was diluted with ethyl acetate (50 mL), saturated aqueous ammonium chloride (10 mL) and water (40 mL). The mixture was partitioned and the organic layer was collected. The aqueous layer was extract with ethyl acetate (40 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated to provide the crude compound. Purification by Preparative Thin Layer Chromatography eluting with 1.8% methanol in dichloromethane, followed by crystallization from methylene chloride/hexanes gave the title compound as a white powder (553 mg, (M+H)+=359, M.P.=173.4-176.4° C.).

Workup

  1. temperatureheated at 120° C. for 15 minutes
  2. customThe mixture was partitioned
  3. customthe organic layer was collected
  4. extractionThe aqueous layer was extract with ethyl acetate (40 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto provide the crude compound
  9. customPurification by Preparative Thin Layer Chromatography
  10. washeluting with 1.8% methanol in dichloromethane
  11. customfollowed by crystallization from methylene chloride/hexanes

Sources & evidence

ORD record
ord-e625996cdeba45a0a11ec5660209e466
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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