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

HRID 1112093Notes

Reaction equation

HRID 1112093 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 2 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 portion 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): δ 7.2-7.72 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 portion of fresh water
  5. dry with materialto dry over magnesium sulfate
  6. customEvaporation of the solvent under reduced pressure

Sources & evidence

ORD record
ord-ac4769bc6a9a4b0095684d091c9a607f
Source dataset
uspto-grants-1978_10
Patent number
US04120856

Reaction notes

Loading…