Toluene → HCID 53862101, compound

HRID 619282Notes

Reaction equation

HRID 619282 reaction equation
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:15]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)(O)[CH2:16][C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[CH:13]=3)[C:8]([CH2:30][CH3:31])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>O.[OH-].[Na+]>[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:15]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[CH:16][C:17]4[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=4)[CH:13]=3)[C:8]([CH2:30][CH3:31])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 15429398HCID 15429398, compound

Product 1

HCID 53862101HCID 53862101, compoundYield 96.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

1.00 g (2.43 mmol, 1.0 equiv) (±)-1-(1-cyclopentyl-3-ethyl-1H-indazol-6-yl)-1-phenyl-2-pyridin-4-yl-ethanol, 578 mg (3.04 mmol, 1.25 equiv) p-toluenesulfonic acid and 25 mL anhydrous toluene were placed in a flask fitted with a Dean-Stark trap and heated to reflux under nitrogen atmosphere. After 7 hours, the reaction mixture was cooled to room temperature and allowed to stir for 72 hours. The reaction mixture was diluted with 200 mL H2O and 100 mL 1N NaOH, and extracted 2×100 mL ethyl acetate. The organic extracts were combined, washed 1×50 mL each H2O, brine, and dried over Na2SO4. Filtration, concentration of filtrate and drying gave a yellow oil, which was purified on a silica gel column (2.5% CH3OH/CH2Cl2) to give 0.92 g (95%) of a white amorphous solid. A small sample was crystallized from ethyl acetate/hexanes to give 27 mg white needles: mp 134-1 36° C.; Anal. calcd for C27H27N3 : C, 82.41; H, 6.92; N, 10.68; Found: C, 82.31; H, 7.17; N, 10.80.

Workup

  1. customfitted with a Dean-Stark trap
  2. temperatureheated
  3. temperatureto reflux under nitrogen atmosphere
  4. extractionextracted 2×100 mL ethyl acetate
  5. washwashed 1×50 mL each H2O, brine
  6. dry with materialdried over Na2SO4
  7. filtrationFiltration, concentration of filtrate
  8. customdrying
  9. customgave a yellow oil, which
  10. customwas purified on a silica gel column (2.5% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-68830dda6ee7436591200641bd414b09
Source dataset
uspto-grants-1999_09
Patent number
US05958953

Reaction notes

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