Ethylene Oxide → Flutazolam

HRID 328497Notes

Reaction equation

HRID 328497 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH2:13][OH:14])[C:10](=[O:15])[CH2:9][N:8]=[C:7]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[F:22])[C:6]=2[CH:23]=1.[CH2:24]1[O:26][CH2:25]1.[OH-].[NH4+]>ClCCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH2:13][OH:14])[C:10](=[O:15])[CH2:9][N:8]3[CH2:24][CH2:25][O:26][C:7]3([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[F:22])[C:6]=2[CH:23]=1

Participants

5

Reactant 3

HCID 6354Ethylene OxideHCID 14923Ammonium HydroxideHCID 30401Ro 07-2750

Product 1

HCID 3398Flutazolam

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 3.3 g (0.01 M) of 7-chloro-1-(2-hydroxyethyl)-5-(2-fluorophenyl)-1,3-dihyrdo-2H-1,4-benzodiazepin-2-one in 40 ml of 1,2-dichloro ethane under nitrogen was treated with 5.2 g (0.02 M) of stannic chloride with stirring. After 20 min, the mixture was cooled in an ice bath and 2.6 g (0.06 M) of ethylene oxide was added. After 1 hr at room temperature, the reaction mixture was made basic with ammonium hydroxide and filtered. The precipitate was washed with dichloromethane, and the combined filtrates were separated. The organic layer was washed with 40 ml of dilute ammonium hydroxide, dried over anhydrous sodium sulfate and evaporated to dryness. The residue was crystallized from a mixture of ether and petroleum ether and recrystallized from toluene to give the above named product as white prisms, mp 142°-147°.

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. waitAfter 1 hr at room temperature
  3. filtrationfiltered
  4. washThe precipitate was washed with dichloromethane
  5. customthe combined filtrates were separated
  6. washThe organic layer was washed with 40 ml of dilute ammonium hydroxide
  7. dry with materialdried over anhydrous sodium sulfate
  8. customevaporated to dryness
  9. customThe residue was crystallized from a mixture of ether and petroleum ether
  10. customrecrystallized from toluene
  11. customto give the above named product as white prisms, mp 142°-147°

Sources & evidence

ORD record
ord-fe4598ec86e340078072f60905b9b3ef
Source dataset
uspto-grants-1977_04
Patent number
US04017532

Reaction notes

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