Sulfuric Acid → HCID 23048179, compound

HRID 1722165Notes

Reaction equation

HRID 1722165 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]3[CH2:23][CH2:22][N:21](C#N)[CH2:20][CH2:19]3)=[N:10]2)=[CH:5][CH:4]=1.OS(O)(=O)=O.[OH-].[Na+]>O>[F:27][C:2]([F:1])([F:26])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]3[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]3)=[N:10]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 14032656HCID 14032656, compound

Product 1

HCID 23048179HCID 23048179, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A stirred mixture of 4-[1-[4-(trifluoromethyl)phenyl]-1H-indazol-3-yl]piperidine-1-carbonitrile of Example 101 (15 g. 0.041 moles) and 25% H2SO4 (100 ml) was refluxed for 20 hours. The mixture was cooled, poured into H2O, and basified with 25% NaOH solution. The product was extracted (dichloromethane), dried (MgSO4), and concentrated to yield 13 g (93%) of 1-[4-(trifluoromethyl)phenyl]-3-(4-piperidinyl)-1H-indazole as an oil. To a stirred mixture of the indazole (4.15 g. 0.012 moles) and triethylamine (3.35 ml. 0.024 moles) in toluene (50 ml) was added acetyl chloride (0.93 ml, 0.013 moles). The reaction was stirred at ambient temperature for 2 hours and then poured into H2O. The product was extracted (CHCl3), dried (MgSO4), and concentrated to yield 4.3 g of an oil. The product was triturated with hexane and then recrystallized from CCl4 -hexane twice to yield 2.80 g of product. The product was further purified using high pressure liquid chromatography (silica gel, ethyl acetate)) to yield 2.1 g (45%) of 1-acetyl-4-[1-[4-(trifluoromethyl)phenyl]-1H-indazol-3-yl]piperidine, m.p. 148°-150° C.

Workup

  1. temperaturewas refluxed for 20 hours
  2. temperatureThe mixture was cooled
  3. extractionThe product was extracted (dichloromethane)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d1e4b8cd2e4f4270b7798f9c4c647f21
Source dataset
uspto-grants-1989_08
Patent number
US04853470

Reaction notes

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