Diazepam → 10-chloro-2,7-dimethyl-2,3,5,11b-tetrahydro-11b-phenyloxazolo[3,2-d][1,4]benzodiazepin-6(7H)-one

HRID 328476

Reaction equation

HRID 328476 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1.[Cl-].[Al+3].[Cl-].[Cl-].[CH2:25]1[O:28][CH:26]1[CH3:27].B(F)(F)F.CCOCC.[OH-].[NH4+]>CCCCCC.C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][N:8]3[CH2:25][CH:26]([CH3:27])[O:28][C:7]3([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1

Participants

8

Reactant 5

HCID 3016DiazepamHCID 6378Propylene OxideHCID 8000Boron trifluoride etherateHCID 14923Ammonium HydroxideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 2140999110-chloro-2,7-dimethyl-2,3,5,11b-tetrahydro-11b-phenyloxazolo[3,2-d][1,4]benzodiazepin-6(7H)-one

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8058HexaneSolvent

Procedure

A mixture of 10.0 g. (35 mmole) of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, 6.7 g. of aluminum chloride, 300 ml. of benzene and 30 ml. of hexane was chilled in an ice-bath and was treated with 10 ml. of propylene oxide. The reaction mixture was warmed to room temperature and was stirred overnight. Work-up as in Method A, Example 5, yielded a mixture of the epimers of 10-chloro-2,7-dimethyl-2,3,5,11b-tetrahydro-11b-phenyloxazole[3,2-d][1,4]benzodiazepin-6(7H)-one. A solution of 1.0 g. of this mixture was stirred overnight at 80° in 25 ml. of boron trifluoride etherate. The reaction mixture was poured carefully into ice water and made basic with ammonium hydroxide. The mixture was extracted with chloroform, water washed, dried and concentrated to a solid residue. Three recrystallizations from methylene chloride-hexane gave the above-titled isomer, m.. 142°-143°.

Workup

  1. additionA mixture of 10.0 g
  2. additionwas treated with 10 ml
  3. customyielded
  4. stirringof this mixture was stirred overnight at 80° in 25 ml
  5. extractionThe mixture was extracted with chloroform, water
  6. washwashed
  7. customdried
  8. concentrationconcentrated to a solid residue
  9. customThree recrystallizations from methylene chloride-hexane
  10. customgave the above-titled isomer, m
  11. custom142°-143°

Sources & evidence

ORD record
ord-4afb1b97b6034dac92faca51bd689ce3
Source dataset
uspto-grants-1977_04
Patent number
US04017531

Linked notes

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