1,3-Dichloroacetone → HCID 21265978, compound

HRID 566290Notes

Reaction equation

HRID 566290 reaction equation
[NH2:1][C:2]1[CH2:8][N:7]=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]2[CH:15]=[C:16]([C:19]([F:22])([F:21])[F:20])[CH:17]=[CH:18][C:4]=2[N:3]=1.Cl[CH2:24][C:25]([CH2:27]Cl)=O.C(=O)([O-])[OH:30].[Na+]>O1CCOCC1>[F:21][C:19]([F:22])([F:20])[C:16]1[CH:17]=[CH:18][C:4]2[N:3]3[CH:27]=[C:25]([CH2:24][OH:30])[N:1]=[C:2]3[CH2:8][N:7]=[C:6]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:5]=2[CH:15]=1

Participants

5

Reactant 3

HCID 107931,3-DichloroacetoneHCID 516892Sodium BicarbonateHCID 15079734HCID 15079734, compound

Product 1

HCID 21265978HCID 21265978, compoundYield 27.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
98 °C

Procedure

A solution of 10.5 g of 2-amino-7-trifluoromethyl-5-phenyl-3H-1,4-benzodiazepine (K. Meguro, H. Tawada & Y. Kuwada, Yakugaku Zasshi, 1973, 93, 1253-1262) and 4.84 g of 1,3-dichloroacetone in 220 ml of dioxan was treated with 2.72 g of anhydrous sodium hydrogen carbonate and stirred at 98° C. for 16 h. After cooling the inorganic salts were filtered off, the filtrate was treated with 0.75 g of p-toluenesulphonic acid and stirred at 98° C. for 2 h. 60 ml of 1N aqueous sodium hydroxide solution were added to this solution and the mixture was stirred at 80° C. for 3 h. After cooling the mixture was concentrated in a vacuum. The residue was taken up in chloroform and water and the aqueous phase was extracted a further four times with chloroform. The chloroform was evaporated in a vacuum. The residue was recrystallized twice from ethyl acetate. There were obtained 3.15 g of 8-trifluoromethyl-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol of m.p. 193-194° C., which was converted into the hydrochloride of m.p. 252-254° C.

Workup

  1. temperatureAfter cooling the inorganic salts
  2. filtrationwere filtered off
  3. additionthe filtrate was treated with 0.75 g of p-toluenesulphonic acid
  4. stirringstirred at 98° C. for 2 h
  5. addition60 ml of 1N aqueous sodium hydroxide solution were added to this solution
  6. stirringthe mixture was stirred at 80° C. for 3 h
  7. temperatureAfter cooling the mixture
  8. concentrationwas concentrated in a vacuum
  9. extractionwater and the aqueous phase was extracted a further four times with chloroform
  10. customThe chloroform was evaporated in a vacuum
  11. customThe residue was recrystallized twice from ethyl acetate

Sources & evidence

ORD record
ord-be5733d169b84536881bd28b7ff900eb
Source dataset
uspto-grants-2001_01
Patent number
US06174881B1

Reaction notes

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