4-Chloroquinoline → 7-Bromo-4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepine

HRID 241163

Reaction equation

HRID 241163 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[CH:5][C:6]2[O:12][CH2:11][CH2:10][NH:9][CH2:8][C:7]=2[CH:13]=1.Cl[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=[CH:17][CH:16]=1.C(N(C(C)C)CC)(C)C>C(O)CCC.C(OCC)(=O)C>[Br:2][C:3]1[CH:4]=[CH:5][C:6]2[O:12][CH2:11][CH2:10][N:9]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[N:18]=[CH:17][CH:16]=3)[CH2:8][C:7]=2[CH:13]=1

Participants

6

Reactant 3

HCID 691404-ChloroquinolineHCID 81531DiisopropylethylamineHCID 668201377-Bromo-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride

Product 1

HCID 668207827-Bromo-4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepineYield 84.6%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 7-bromo-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride (1.50 g, 5.67 mmol) (example 2, step 1), 4-chloroquinoline (0.973 g, 5.95 mmol), diisopropylethylamine (2.93 g, 22.7 mmol) in 1-butanol (15 mL) was stirred at 170° C. for 1 hour in a microwave synthesizer. The reaction mixture was diluted with ethyl acetate (100 mL), washed with saturated sodium bicarbonate (50 mL) and brine (50 mL), dried over sodium sulfate. Filtration and concentration afforded a crude brown oil that was purified by silica gel chromatography (9:1 dichloromethane/methanol) to provide 7-bromo-4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepine (1.70 g, 84.6% yield) as a yellow oil. MS (EI) for C18H15BrN2O: 356 (MH+).

Workup

  1. washwashed with saturated sodium bicarbonate (50 mL) and brine (50 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationFiltration and concentration
  4. customafforded a crude brown oil that
  5. customwas purified by silica gel chromatography (9:1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-d7389744bcd647fc8245228d7df8eec0
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Linked notes

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