Water → 1-(2,2,2-Trifluoroethyl)-5-phenyl-1H-1,4-benzodiazepine-2(3H)-one

HRID 609717Notes

Reaction equation

HRID 609717 reaction equation
[C:1]1([C:7]2[N:8]=[CH:9][C:10](=[O:18])[N:11]=[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=23)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:25][C:26]([F:30])([F:29])[CH2:27]I.O>CN(C=O)C>[F:25][C:26]([F:30])([F:29])[CH2:27][N:11]1[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:8][CH2:9][C:10]1=[O:18]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 195994005-Phenyl-1,4-benzodiazepin-2-one

Product 1

HCID 111416741-(2,2,2-Trifluoroethyl)-5-phenyl-1H-1,4-benzodiazepine-2(3H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-phenyl-1,4-benzodiazepine-2-one (50 g, 0.211 mole) in DMF (100 mL) was treated with cesium carbonate (103.5 g, 0.317 mole) and trifluoroethyl iodide (109.7 g, 0.525 mole). The mixture was stirred at 50° C.-60° C. overnight. The reaction mixture was then poured into water (2 L) and extracted with ethyl acetate (3×1 L). The combined ethyl acetate fractions were dried over anhydrous magnesium sulfate, filtered and concentrated at reduced pressure. The material was chromatographed on silica gel (1.5 Kg) eluting with 1:1 ethyl acetate/heaxane. The combined pure fractions were concentrated at reduced pressure. The residue was swished with warm ethyl ether, cooled and filtered to give the product. MP=130-131° C.; 1H NMR CDCl3, δ7.65-7.60 (m, 2H), 7.60-7.45 (m, 5H), 7.40-7.20(m, 2H), 5.25 (dq, J=14, 8.6 Hz, 1H), 4.82(d, J=10.5 Hz, 1H), 4.15 (app sextet, J=8.6 Hz, 1H), 3.81 (d, J=10.5 Hz, 1H).

Workup

  1. extractionextracted with ethyl acetate (3×1 L)
  2. dry with materialThe combined ethyl acetate fractions were dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated at reduced pressure
  5. customThe material was chromatographed on silica gel (1.5 Kg)
  6. washeluting with 1:1 ethyl acetate/heaxane
  7. concentrationThe combined pure fractions were concentrated at reduced pressure
  8. temperaturecooled
  9. filtrationfiltered
  10. customto give the product

Sources & evidence

ORD record
ord-a10f9c67c1d6405f989d963f4e0575ba
Source dataset
uspto-grants-1999_12
Patent number
US05998407

Reaction notes

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