Sulfuric Acid → HCID 22397358, compound

HRID 1382613Notes

Reaction equation

HRID 1382613 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH:17]3[CH2:22][CH2:21][N:20](C#N)[CH2:19][CH2:18]3)=[N:9]2)=[CH:4][CH:3]=1.OS(O)(=O)=O.[OH-].[Na+]>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 14032657HCID 14032657, compound

Product 1

HCID 22397358HCID 22397358, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A stirred mixture of 4-[1-(4-fluorophenyl)-1H-indazol-3-yl]piperidine-1-carbonitrile of Example 102 (30 g, 0.094 moles) and 25% H2SO4 (225 ml) was refluxed for 20 hours. The mixture was cooled, poured into H2O, and basified with a 25% NaOH solution. The product was extracted (dichloromethane), dried (MgSO4), and concentrated to yield 21 g (76%) of 1-(4-fluorophenyl)-3-(4-piperidinyl)-1H-indazole as an oil. To a stirred suspension of the indazole (3.5 g, 0.012 moles) and triethylamine (3.3 ml, 0.024 moles) in toluene (50 ml) was added methyl chloroformate (1.0 ml, 0.013 moles). The mixture was stirred for 17 hours at ambient temperature and was then poured into H2O. The product was extracted (ethyl acetate), dried (Mg SO4), and concentrated to yield 4.6 g of an oil. The product was purified on the HPLC (silica gel:ethyl acetate-hexane, 1:2) which produced 3.0 g (72%) of 4-[1-(4-fluorophenyl)-1H-indazol-3-yl]piperidine-1-carboxylic acid methyl ester, m.p. 95°-97° 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-c7a84b61210a44be8391ca12ee6d9501
Source dataset
uspto-grants-1989_02
Patent number
US04806649

Reaction notes

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