Phosphorus trichloride → 3-Fluoro-1,3-dihydro-1-methyl-7-chloro-5-phenyl-2H-1,4-benzodiazepin-2-one

HRID 2051781Notes

Reaction equation

HRID 2051781 reaction equation
P(Cl)(Cl)Cl.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[N:15]([CH3:16])[C:14](=[O:17])[CH:13]([F:18])[N+:12]([O-])=[C:11]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]=2[CH:26]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[N:15]([CH3:16])[C:14](=[O:17])[CH:13]([F:18])[N:12]=[C:11]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]=2[CH:26]=1

Participants

5

Reactant 3

HCID 24387Phosphorus trichlorideHCID 516892Sodium BicarbonateHCID 132225697-chloro-3-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide

Product 1

HCID 126021203-Fluoro-1,3-dihydro-1-methyl-7-chloro-5-phenyl-2H-1,4-benzodiazepin-2-oneYield 65.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 580 μl (6.6 mmole) of phosphorous trichloride was added to a solution of 1.05 g (3.3 mmole) of 7-chloro-3-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide in 15 ml methylene chloride at 5°. The solution was stirred for 2 hr at 5° and then 20 hr at 25°, and then poured into 100 ml of cold aqueous 5% sodium bicarbonate solution. The organic layer was separated, washed with water, dried (MgSO4) and evaporated to dryness to give 800 mg (80%) of crude product. Recrystallization from heptane gave 650 mg (65%) of 7-chloro-3-fluoro-1.3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one as colorless crystals, mp 139°-140°. Even under these mild conditions, an appreciable amount of 3,7-dichloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one is formed as an impurity. If the reaction mixture is heated to 61° C. for only 10 min., none of the desired 3-fluoro compound is formed.

Workup

  1. customThe organic layer was separated
  2. washwashed with water
  3. dry with materialdried (MgSO4)
  4. customevaporated to dryness
  5. customto give 800 mg (80%) of crude product
  6. customRecrystallization from heptane

Sources & evidence

ORD record
ord-68d02bdcb19b4c9e9754ec527e16c0d0
Source dataset
uspto-grants-1980_01
Patent number
US04182760

Reaction notes

Loading…