p-Toluenesulfonic acid monohydrate → HCID 21877772, compound

HRID 1991270Notes

Reaction equation

HRID 1991270 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[CH:13]=[C:12]([F:14])[C:11]([C:15]3(O)[CH2:20][CH2:19][S:18][CH2:17][CH2:16]3)=[C:10]([F:22])[CH:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[S:18]1[CH2:17][CH:16]=[C:15]([C:11]2[C:12]([F:14])=[CH:13][C:8]([N:3]3[C:2]([CH3:1])=[CH:6][CH:5]=[C:4]3[CH3:7])=[CH:9][C:10]=2[F:22])[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrate2×HCID 21877813HCID 21877813, compound

Product 1

HCID 21877772HCID 21877772, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A stirred solution of 4-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-2,6-difluorophenyl]tetrahydro-2H-thiopyran-4-ol (Step 2, 1.617 g, 5.00 mmol) and p-toluenesulfonic acid monohydrate (0.107 g) in benzene (20 mL) is heated at reflux using a Dean-Stark trap for 5 h, during which additional p-toluenesulfonic acid monohydrate (0.342 g) is added. Solvent is then removed under reduced pressure, and the residue is taken up in CH2Cl2 (60 mL), washed with saturated aqueous NaHCO3 (2×20 mL) and water (3×20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 2-5% EtOAc/Hexanes, affords the title compound, mp 118-119° C.; MS (ESI+) for C17H17F2NS m/z 306 (M+H)+.

Workup

  1. temperatureat reflux
  2. customfor 5 h
  3. customSolvent is then removed under reduced pressure
  4. washwashed with saturated aqueous NaHCO3 (2×20 mL) and water (3×20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by chromatography on a Biotage Flash 40M 90 g silica gel cartridge
  8. washeluting with 2-5% EtOAc/Hexanes

Sources & evidence

ORD record
ord-1053daa0475c48679e32997b1153083f
Source dataset
uspto-grants-2010_01
Patent number
US07645781B2

Reaction notes

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