Phenyl chloroformate → HCID 21497568, compound

HRID 1730408Notes

Reaction equation

HRID 1730408 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15][N:16](C)[CH3:17])=[CH:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])[C:6]=2[CH:26]=1.C(=O)(O)[O-].[K+].ClC(OC1C=CC=CC=1)=O>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15][NH:16][CH3:17])=[CH:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])[C:6]=2[CH:26]=1

Participants

5

Reactant 3

HCID 15891Phenyl chloroformateHCID 516893Potassium BicarbonateHCID 12707091HCID 12707091, compound

Product 1

HCID 21497568HCID 21497568, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A stirred suspension of 8-chloro-6-(o-chlorophenyl)-1-[(dimethylamino)methyl]-4H-imidazo[1,2-a][1,4]benzodiazepine (3.95 g, 10 mmole) and potassium bicarbonate (17 g, 17 mmole) in 280 ml. of chloroform is treated with phenyl chloroformate (12.97 g, 87 mmole) and refluxed for 50 hours. The resulting mixture is cooled, washed with water (100 ml) and the solvent is removed in vacuo. The residue is dissolved in 170 ml. of methanol and the resulting solutionis treated with 100 ml. of 5.6 g of potassium hydroxide and 10 g of potassium bicarbonate. This mixture is stirred under nitrogen for 24 hours, acidified with concentrated hydrochloric acid, diluted with water, and extracted with 500 ml. of ether. The ether phase is dried over anhydrous sodium sulfate, and the ether is removed in vacuo. The thus obtained material is dissolved in a mixture of 800 ml. of ethanol and aqueous 50% potassium hydroxide (200 ml) and refluxed under nitrogen for 24 hours. This solution is treated with 200 ml. of concentrated hydrochloric acid and the ethanol is removed in vacuo. The remaining aqueous phase is extracted with ether, and the ether is discarded. The aqueous phase is then made basic, pH 9.0 and re-extracted with methylene chloride (800 ml). The methylene chloride is dried over anhydrous sodium sulfate and the solvent is removed in vacuo. The resulting oil is crystallized to give 8-chloro-6-(o-chlorophenyl)-1-[(methylamino)methyl]-4H-imidazo[1,2-a][1,4]benzodiazepine.

Workup

  1. temperaturerefluxed for 50 hours
  2. temperatureThe resulting mixture is cooled
  3. washwashed with water (100 ml)
  4. customthe solvent is removed in vacuo
  5. dissolutionThe residue is dissolved in 170 ml
  6. additionof methanol and the resulting solutionis treated with 100 ml
  7. additiondiluted with water
  8. extractionextracted with 500 ml
  9. dry with materialThe ether phase is dried over anhydrous sodium sulfate
  10. customthe ether is removed in vacuo
  11. dissolutionThe thus obtained material is dissolved in a mixture of 800 ml
  12. temperatureof ethanol and aqueous 50% potassium hydroxide (200 ml) and refluxed under nitrogen for 24 hours
  13. additionThis solution is treated with 200 ml
  14. customof concentrated hydrochloric acid and the ethanol is removed in vacuo
  15. extractionThe remaining aqueous phase is extracted with ether
  16. extractionpH 9.0 and re-extracted with methylene chloride (800 ml)
  17. dry with materialThe methylene chloride is dried over anhydrous sodium sulfate
  18. customthe solvent is removed in vacuo
  19. customThe resulting oil is crystallized

Sources & evidence

ORD record
ord-f944df8ab9564d7388ed48a2035825d7
Source dataset
uspto-grants-1976_11
Patent number
US03992408

Reaction notes

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