Norfludiazepam → HCID 14909583, compound

HRID 1658600Notes

Reaction equation

HRID 1658600 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[C:6]=2[CH:20]=1.[Cl-].[Al+3].[Cl-].[Cl-].[CH2:25]1[O:27][CH2:26]1>C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]3[CH2:25][CH2:26][O:27][C:7]3([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 4540NorfludiazepamHCID 6354Ethylene Oxide2×HCID 6451240Aluminum(III) Chloride2×

Product 1

HCID 14909583HCID 14909583, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To 15 g. (51.9 mmole) of 7-chloro-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 150 ml. of dry benzene, 9 g. (67.7 mmole) of aluminum chloride was added and stirring was continued 15 minutes. The reaction mixture was cooled in an ice bath and 8.8 g. (0.2 mole) of ethylene oxide was added dropwise. After 18 hours of stirring at room temperature, the reaction mixture was heated to 40° for 1 hour and then cooled to room temperature and treated with 5 g. (37.6 mmole) of aluminum chloride, followed by 4.4 g. (0.1 mole) of ethylene oxide. The reaction mixture was heated 4 hours at 45°-50° and then evaporated to dryness. ethylene chloride, ice and ammonium hydroxide were added and the solid removed by filtration. The filtrate was separated and the organic phase reduced to dryness in vacuo. The residue was dissolved in dilute hydrochloric acid and the pH of the solution adjusted to 5 with ammonium hydroxide. The acidic solution was washed with ether, made basic and extracted with methylene chloride. The organic phase was washed with brine, dried and evaporated to dryness. Recrystallization from methylene chloride-hexane gave the above-titled product as colorless rods, m.p. 183°-184°.

Workup

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. stirringAfter 18 hours of stirring at room temperature
  3. temperaturethe reaction mixture was heated to 40° for 1 hour
  4. additiontreated with 5 g
  5. temperatureThe reaction mixture was heated 4 hours at 45°-50°
  6. customevaporated to dryness
  7. additionethylene chloride, ice and ammonium hydroxide were added
  8. customthe solid removed by filtration
  9. customThe filtrate was separated
  10. dissolutionThe residue was dissolved in dilute hydrochloric acid
  11. washThe acidic solution was washed with ether
  12. extractionextracted with methylene chloride
  13. washThe organic phase was washed with brine
  14. customdried
  15. customevaporated to dryness
  16. customRecrystallization from methylene chloride-hexane

Sources & evidence

ORD record
ord-e67b31c42b96482eb5ee80a14c622b28
Source dataset
uspto-grants-1976_06
Patent number
US03965151

Reaction notes

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