p-Toluenesulfonic acid monohydrate → HCID 17968162, compound

HRID 271570Notes

Reaction equation

HRID 271570 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:13][C:14]1[CH:19]=[C:18]([O:20][CH2:21][CH2:22][O:23]C2CCCCO2)[CH:17]=[CH:16][C:15]=1[N:30]1[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]1>CO>[F:13][C:14]1[CH:19]=[C:18]([CH:17]=[CH:16][C:15]=1[N:30]1[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]1)[O:20][CH2:21][CH2:22][OH:23]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 59834606HCID 59834606, compound

Product 1

HCID 17968162HCID 17968162, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

p-Toluenesulfonic acid monohydrate (45.2 mmol) is added to 4-{2-fluoro-4-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-piperazine-1-carboxylic acid, tert.-butyl ester (22.6 mmol) in MeOH (50 ml) at room temperature. The reaction mixture is stirred at room temperature for 1.5 h. After the mixture is extracted with AcOEt, the organic layer is washed with brine, dried over magnesium sulfate and filtered. The solvent is evaporated. To the residue in CH2Cl2 (9 ml), TFA (17.5 ml) is added at 0° C. The reaction mixture is stirred at room temperature for 1 h. The solvent is removed by evaporation and dried to give brown crude oily product, 2-(3-fluoro-4-piperazin-1-yl-phenoxy)-ethanol. To the crude product in DMF (100 ml), potassium carbonate (113 mmol) is successively added at 0° C. The mixture is stirred at 0° C. for 15 min. 6-Bromomethyl-7-(2,2-dimethyl-propyl)-7.H.-pyrrolo[2,3-.d.]pyrimidine-2-carbonitrile (22.6 mmol) is added to the mixture at 0° C. The reaction mixture is stirred at room temperature for 3 h and quenched with saturated ammonium chloride. The mixture is extracted with AcOEt. The combined extracts are washed with H2O, brine and dried over magnesium sulfate. The solvent is evaporated and the residue is purified by column chromatography on silica gel using n-hexane:AcOEt=3:2 (v/v).

Workup

  1. extractionAfter the mixture is extracted with AcOEt
  2. washthe organic layer is washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent is evaporated
  6. additionTo the residue in CH2Cl2 (9 ml), TFA (17.5 ml) is added at 0° C
  7. stirringThe reaction mixture is stirred at room temperature for 1 h
  8. customThe solvent is removed by evaporation
  9. customdried

Sources & evidence

ORD record
ord-cce431ff67ad40e3b4eb6420d319c9f8
Source dataset
uspto-grants-2008_11
Patent number
US07452886B2

Reaction notes

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