Ethyl Acetate → 4-(6-Isopropyl-quinolin-8-yl)[1,4]-diazepan-1-carboxylic acid tert-butyl ester

HRID 532853Notes

Reaction equation

HRID 532853 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]([CH3:14])[CH3:13])[CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].CC([O-])(C)C.[K+].CCOC(C)=O>COCCOC>[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][CH2:26][N:25]([C:2]2[CH:3]=[C:4]([CH:12]([CH3:14])[CH3:13])[CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 218655558-Bromo-6-(propan-2-yl)quinolineHCID 23665647Potassium tert-butoxide

Product 1

HCID 593661634-(6-Isopropyl-quinolin-8-yl)[1,4]-diazepan-1-carboxylic acid tert-butyl esterYield 66.5%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 8-Bromo-6-isopropyl-quinoline (1.38 g, 5.51 mmol, 1.04 equiv) and 1-(tert-butoxycarbonyl)homopiperazine (1.06 g, 1.0 equiv) in 5.5 mL of DME was degassed with compressed nitrogen gas for 5 minutes. To the mixture was added t-BuOK (0.83 g, 1.4 equiv). After degassing for another 2 minutes, allylchloro[1,3-(2,6-di-isopropylphenyl)imidazol-2-ylidene]palladium (II) (Nolan's catalyst, 61 mg, 0.02 equiv) was added and the resulting mixture was heated to 60° C. overnight, then cooled down to room temperature. EtOAc (˜70 mL) was added and the mixture was filtered through celite. The filtrate was washed with saturated aqueous NaHCO3 (70 mL) and brine (70 mL), dried over magnesium sulfate and concentrated. The residue was purified by silica gel chromatography using 5% to 20% EtOAc in hexane to afford the title compound (1.3 g, 64%). MS (ES) m/z 370.2 (M+H+).

Workup

  1. customwas degassed with compressed nitrogen gas for 5 minutes
  2. customAfter degassing for another 2 minutes
  3. temperaturecooled down to room temperature
  4. filtrationthe mixture was filtered through celite
  5. washThe filtrate was washed with saturated aqueous NaHCO3 (70 mL) and brine (70 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3a7ddb2ffea54829b6af326d3bef80e8
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

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