Trifluoroacetic acid → 3-Hydroxy-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine

HRID 1867574Notes

Reaction equation

HRID 1867574 reaction equation
BrN1C(=[O:7])CCC1=O.[O:9]=[C:10]1[CH2:16][N:15]=[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:13]2[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=2[N:11]1[CH2:27][C:28]([F:31])([F:30])[F:29].FC(F)(F)C(O)=O>C(Cl)(Cl)(Cl)Cl>[OH:7][CH:16]1[N:15]=[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:13]2[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=2[N:11]([CH2:27][C:28]([F:31])([F:29])[F:30])[C:10]1=[O:9]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 67184N-bromobutanimideHCID 111416741-(2,2,2-Trifluoroethyl)-5-phenyl-1H-1,4-benzodiazepine-2(3H)-one

Product 1

HCID 184442523-Hydroxy-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

N-Bromosuccinimide (0.335 g, 1.88 mmol) was added to a solution of 2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine (H. G. Selnick et al., J. Med. Chem., 1997, 40, 3865-3868) (0.500 g, 1.57 mmol) in carbon tetrachloride (20 mL) at room temperature. After 15 min, trifluoroacetic acid (1.0 mL) was added, and the reaction refluxed for 5 h. The reaction was cooled and concentrated. The residue was dissolved in 5% aqueous sodium acetate (15 mL) and acetone (10 mL) and stirred overnight. The reaction was concentrated and worked up, and the crude product purified by chromatography (silica gel, 0-30% ethyl acetate in hexane gradient elution), providing the title compound. MS 335 (M+1) 1H NMR (500 MHz, CDCl3) □ 7.92-7.30 (9H, m), 5.21 (dq, J=15, 8 Hz, 1H), 5.07 (d, J=10 Hz, 0.5H), 4.51 (d, J=10 Hz, 0.5H), 4.22 (t, dq, J=15, 8 Hz, 1H).

Workup

  1. temperaturethe reaction refluxed for 5 h
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in 5% aqueous sodium acetate (15 mL)
  5. concentrationThe reaction was concentrated
  6. customthe crude product purified by chromatography (silica gel, 0-30% ethyl acetate in hexane gradient elution)

Sources & evidence

ORD record
ord-a846472c65ad4f18ac8cde24b8abb197
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

Loading…