Trimethylaluminum → 7-bromo-4-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-6-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one

HRID 577571Notes

Reaction equation

HRID 577571 reaction equation
[Br:1][C:2]1[C:3]([CH3:26])=[C:4]([C:9]([O:12][CH2:13][CH2:14][NH:15][CH2:16][C:17]2[C:18](=[O:25])[NH:19][C:20]([CH3:24])=[CH:21][C:22]=2[CH3:23])=[CH:10][CH:11]=1)[C:5](OC)=[O:6].C[Al](C)C>O1CCOCC1>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[O:12][CH2:13][CH2:14][N:15]([CH2:16][C:17]3[C:18](=[O:25])[NH:19][C:20]([CH3:24])=[CH:21][C:22]=3[CH3:23])[C:5](=[O:6])[C:4]=2[C:3]=1[CH3:26]

Participants

4

Reactant 2

HCID 16682925TrimethylaluminumHCID 86723798Methyl 3-bromo-6-(2-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]amino}ethoxy)-2-methylbenzoate

Product 1

HCID 867237977-bromo-4-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-6-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-oneYield 29%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of methyl 3-bromo-6-(2-{[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]amino}ethoxy)-2-methylbenzoate (126c, 134 mg, 0.317 mmol) in 1,4-dioxane (1 mL) was added trimethylaluminum (2.0M in heptanes, 32.0 mg, 0.440 mmol). The reaction mixture was stirred at room temperature for 30 minutes, heated at 55° C. for 2 hours, and then 75° C. for 4 hours. The reaction mixture was cooled to room temperature, the solvent removed under vacuum, and the residue was stirred vigorously with EtOAc (25 mL) and 10% aq. solution of Rochell's salts. Once the mixture became homogeneous, the layers were separated and the organic layer was purified directly by column chromatography (silica gel, (7N NH3 in MeOH) in EtOAc) to give 7-bromo-4-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-6-methyl-3,4-dihydro-1,4-benzoxazepin-5(2H)-one (126d, 36 mg, 27% yield) as a light tan solid.

Workup

  1. temperatureheated at 55° C. for 2 hours
  2. wait75° C. for 4 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe solvent removed under vacuum
  5. stirringthe residue was stirred vigorously with EtOAc (25 mL) and 10% aq. solution of Rochell's salts
  6. customthe layers were separated
  7. customthe organic layer was purified directly by column chromatography (silica gel, (7N NH3 in MeOH) in EtOAc)

Sources & evidence

ORD record
ord-c10bea724bbb4b0e9c2bb05e5badc837
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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