Toluene → 4-(2,4-Dimethylphenyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 2411223Notes

Reaction equation

HRID 2411223 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH3:9].[C:10]([N:17]1[CH2:23][CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:13]([O:12][C:10]([N:17]1[CH2:23][CH2:22][CH2:21][N:20]([C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=2[CH3:9])[CH2:19][CH2:18]1)=[O:11])([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 4

HCID 1140TolueneHCID 68503Benzene, 1-bromo-2,4-dimethyl-HCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 673808924-(2,4-Dimethylphenyl)-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 71.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolvent

Procedure

To a mixture of 1-bromo-2,4-dimethylbenzene (1.85 g), 1-Boc-[1,4]diazepane (2 g), palladium(II) acetate (0.12 g), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.31 g) and sodium tert-butoxide (1.34 g) was added toluene (35 mL), and the mixture was stirred with heating under reflux for 9 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (chloroform:methanol) to give 4-(2,4-dimethylphenyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (2.16 g). The obtained 4-(2,4-dimethylphenyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (2.16 g) was dissolved in chloroform (17 mL), 4N hydrogen chloride/ethyl acetate solution (6.9 mL) was added, and the mixture was stirred at room temperature overnight. The solvent was evaporated from the reaction mixture to give the title compound (1.74 g).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 9 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-f483749e08674f5295303218093b4dac
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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