Dichloromethane → 9-Chloro-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine

HRID 459894Notes

Reaction equation

HRID 459894 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]([F:12])([F:11])[CH2:9]I.[Cl:13][C:14]1[C:24]2[NH:23][C:22](=[O:25])[CH2:21][N:20]=[C:19]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:18]=2[CH:17]=[CH:16][CH:15]=1.C(Cl)Cl>CN(C)C=O.[Cl-].[Na+].O>[Cl:13][C:14]1[C:24]2[N:23]([CH2:9][C:8]([F:12])([F:11])[F:7])[C:22](=[O:25])[CH2:21][N:20]=[C:19]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:18]=2[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 677091,1,1-Trifluoro-2-iodoethane2×HCID 184442579-Chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Product 1

HCID 184442569-Chloro-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepineYield 39.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

Cesium carbonate (1.01 g, 3.08 mmol) was added to a solution of 2,2,2, -trifluoroethyl iodide (0.991 mL, 10.3 mmol) and 9-chloro-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine (0.557 g, 2.06 mmol) in dimethylformamide. The reaction was heated at 50° C. for 96 h, adding more 2,2,2-trifluoroethyl iodide as needed. The reaction was worked up with methylene chloride and saturated brine. The residue was purified by chromatography (silica gel, 0–30% ethyl acetate in hexane gradient elution), giving the title compound (287 mg). 1H NMR (500 MHz, CDCl3) δ 7.66–7.23 (m, 8H), 5.20 (m, 1H), 4.85 (d, J=11 Hz, 1H), 4.24 (m, 1H), 3.79 (d, J=11 Hz, 1H).

Workup

  1. customThe residue was purified by chromatography (silica gel, 0–30% ethyl acetate in hexane gradient elution)

Sources & evidence

ORD record
ord-270730601e794e078b7cd7c997650408
Source dataset
uspto-grants-2007_03
Patent number
US07196079B2

Reaction notes

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