Benzene, 1-chloro-4-fluoro- → HCID 14032529, compound

HRID 867688Notes

Reaction equation

HRID 867688 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][N:11]=2)[CH2:6][CH2:5]1.F[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1.[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31]>CN(C)C=O.CCOCC.O>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31].[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([N:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:10]([CH:7]3[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]3)=[N:11]2)=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 9604Benzene, 1-chloro-4-fluoro-HCID 24758Sodium hydrideHCID 444972Fumaric AcidHCID 178480237HCID 178480237, compound

Product 1

HCID 14032529HCID 14032529, compoundYield 47.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of 1.1 g of sodium hydride (50% oil dispersion) in 40 ml of dimethylformamide was added, dropwise, under nitrogen, 4.0 g of 3-(1-methyl-4-piperidinyl)-1H-indazole dissolved in 25 ml of hot dimethylformamide. The reaction was stirred at ambient temperature for 45 min, and 2.9 ml of 4-fluorochlorobenzene was added. The temperature was increased to 120° and the reaction proceeded at this temperature for 24 hr. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was heated (steam bath) with 3N hydrochloric acid and the salt was collected. The salt was immediately recrystallized from water. The wet salt was treated with ammonium hydroxide and the base was extracted into dichloromethane. Evaporation of the dichloromethane in vacuo gave an oil. The oil solidified on standing. The solid was dissolved in ether and 1.4 g of fumaric acid was added. Recrystallization from 2-propanol gave 3.9 g (47.5%) of product, mp 176°-178° C.

Workup

  1. additionwas added
  2. temperatureThe temperature was increased to 120°
  3. waitthe reaction proceeded at this temperature for 24 hr
  4. extractionthe aqueous mixture was extracted with ethyl acetate
  5. extractionThe ethyl acetate extract
  6. washwas washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customevaporated in vacuo
  9. temperatureThe residue was heated (steam bath) with 3N hydrochloric acid
  10. customthe salt was collected
  11. customThe salt was immediately recrystallized from water
  12. additionThe wet salt was treated with ammonium hydroxide
  13. extractionthe base was extracted into dichloromethane
  14. customEvaporation of the dichloromethane in vacuo
  15. customgave an oil
  16. customRecrystallization from 2-propanol

Sources & evidence

ORD record
ord-195cb681bbff4c8f898cebc895be9466
Source dataset
uspto-grants-1988_10
Patent number
US04775761

Reaction notes

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