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

HRID 1389809Notes

Reaction equation

HRID 1389809 reaction equation
[F:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:5]=2[NH:4][C:3]1=[O:20].[CH3:21]I.[H-].[Na+].[H][H]>C1COCC1.C(Cl)Cl.O>[F:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:6]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:5]=2[N:4]([CH3:21])[C:3]1=[O:20]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 131259877-Chloro-3-fluoro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 126021203-Fluoro-1,3-dihydro-1-methyl-7-chloro-5-phenyl-2H-1,4-benzodiazepin-2-oneYield 45.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a well stirred solution of 3.0 g (0.01 mol) of 3-fluoro-1,3-dihydro-7-chloro-5-phenyl-2H-1,4-benzodiazepin-2-one, 75 ml of dry THF and 25.56 g (0.18 mol, 11.2 ml) of methyl iodide was added a suspension of 0.48 g (0.02 mol) of sodium hydride in 20 ml of THF. There was an immediate evolution of hydrogen. The contents of the flask were stirred under a nitrogen atmosphere for exactly two hours. The product mixture was poured into approximately 100 ml of water and methylene chloride added to extract the product. The organic layer was separated and washed twice with ca. 50 ml portions of fresh water, and then allowed to dry over magnesium sulfate. Evaporation of the solvent under reduced pressure gave 1.38 g of a yellow crystalline material. Recrystallization from hot heptane gave 0.97 g of an off-white powder identified as 3-fluoro-1-(N-methyl)-7-chloro-5-phenyl-1,4-benzodiazepin-2-one: 1H nmr (DMSO-d6): δ7.2-7.72 ppm (m, 8H), δ 5.8 ppm (d, 1H, 56 Hz), δ 3.37 (m, 3H, N-methyl); 19F nmr (DMSO-d6) δ -160.14 ppm (d, J=56 Hz).

Workup

  1. additionadded
  2. extractionto extract the product
  3. customThe organic layer was separated
  4. washwashed twice with ca. 50 ml portions of fresh water
  5. dry with materialto dry over magnesium sulfate
  6. customEvaporation of the solvent under reduced pressure

Sources & evidence

ORD record
ord-db571f6648e846e98022fa4c1aaab039
Source dataset
uspto-grants-1981_01
Patent number
US04246270

Reaction notes

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