Sodium Carbonate → Methyl 3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoate

HRID 14030Notes

Reaction equation

HRID 14030 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([C:10]([N:12]([CH2:16][CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])=[O:11])[CH:7]=[C:6](Br)[CH:5]=1.[N:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][C:29]=2B(O)O)[CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:13]([N:12]([CH2:16][CH2:17][CH3:18])[C:10]([C:8]1[CH:9]=[C:4]([CH:5]=[C:6]([C:29]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:30]=2[N:21]=[CH:22][CH:23]=[CH:24]3)[CH:7]=1)[C:3]([O:2][CH3:1])=[O:20])=[O:11])[CH2:14][CH3:15]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343808-Quinolineboronic acidHCID 21939662Methyl 3-bromo-5-(dipropylcarbamoyl)benzoate

Product 1

HCID 21086177Methyl 3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoateYield 77.7%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
22.5 °C

Procedure

A mixture of methyl-3-bromo-5-[(dipropylamino)carbonyl]benzoate (XLVIII, 200 mg, 0.58 mmol), 8-quinolineboronic acid (200.6 mg, 1.2 mmol), sodium carbonate (870 Micro Liter of a 2 M mixture in water, 1.74 mmol) in toluene (6 mL) is degassed under reduced pressure for 15 minutes and purged with argon. Palladium tetrakis(triphenylphosphine) (139 mg, 0.12 mmol) is added and the reaction mixture is degassed under reduced pressure for 15 minutes and purged with argon. The reaction mixture is heated at reflux overnight, cooled to 20-25 degrees C. and diluted with chloroform. The organic phase is separated and washed with water (3×50 mL), and saline, dried over sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (silica, ethyl acetate/hexanes, 1.3/1) gives methyl 3-[(dipropylamino)carbonyl]-5-(8-quinolinyl)benzoate (XLIX, 176 mg), NMR (300 MHz, CDCl3): delta 8.91, 8.42, 8.21, 8.09, 7.95, 7.86, 7.77, 7.64, 3.94, 3.49, 3.34, 1.64, 0.99 and 0.84.

Workup

  1. customis degassed under reduced pressure for 15 minutes
  2. custompurged with argon
  3. customthe reaction mixture is degassed under reduced pressure for 15 minutes
  4. custompurged with argon
  5. temperatureThe reaction mixture is heated
  6. temperatureat reflux overnight
  7. additionand diluted with chloroform
  8. customThe organic phase is separated
  9. washwashed with water (3×50 mL), and saline
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customPurification by flash column chromatography (silica, ethyl acetate/hexanes, 1.3/1)

Sources & evidence

ORD record
ord-27a27eb7f74f4614aace5ce27cfbf3e5
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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