Water → 3-fluoro-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

HRID 1389820Notes

Reaction equation

HRID 1389820 reaction equation
[F:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])[C:6]2[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:5]=2[NH:4][C:3]1=[O:21].CI.O.[CH3:25]CCCCC>O1CCCC1.C1C=CC=CC=1>[F:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])[C:6]2[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:5]=2[N:4]([CH3:25])[C:3]1=[O:21]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 8058HexaneHCID 131259933-fluoro-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Product 1

HCID 131259993-fluoro-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (0.25 g of 50% mineral oil emulsion washed twice with tetrahydrofuran, 0.0050 mole) in 10 ml tetrahydrofuran was added portionwise at ambient temperature to a well stirred solution of 1.7 g (0.0053 mole) 3-fluoro-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one and 5.6 g (0.039 mole) methyl iodide in 50 ml tetrahydrofuran under nitrogen. The solution was stirred 2 hr at room temperature, then poured into 100 ml water. The product was extracted with methylene chloride, the extract dried over MgSO4 and the solvent evaporated, yielding a tan solid. The crude product was dissolved in benzene and allowed to crystallize giving a white solid; a second crop was obtained by addition of n-hexane, yielding a total of 1.1 g of 3-fluoro-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one: mp 204°-205°; 1H nmr (DMSO-d6) δ 7.6 ppm (m, 6 H), δ 7.0 ppm (m, 1H), δ 5.94 ppm (d, 56 Hz, 1H), δ 3.45 ppm (s, 3H); 19F nmr (DMSO-d6) δ -161.8 ppm (d, J=56 Hz).

Workup

  1. washSodium hydride (0.25 g of 50% mineral oil emulsion washed twice with tetrahydrofuran, 0.0050 mole) in 10 ml tetrahydrofuran
  2. additionwas added portionwise at ambient temperature to a well
  3. extractionThe product was extracted with methylene chloride
  4. dry with materialthe extract dried over MgSO4
  5. customthe solvent evaporated
  6. customyielding a tan solid
  7. customto crystallize
  8. customgiving a white solid

Sources & evidence

ORD record
ord-9dfdc362f49a4e44b588bb98d01dd4e4
Source dataset
uspto-grants-1981_01
Patent number
US04246270

Reaction notes

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