1,2-Dimethoxyethane → N-[2-(6-bromo-2-pyridinyl)-4-methylphenyl]-2,2-dimethylpropanamide

HRID 1780585Notes

Reaction equation

HRID 1780585 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.C(COC)OC.B([C:18]1[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=1[NH:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])(O)O.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.[Cl-].[Cl-].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+2]>[Br:8][C:4]1[N:3]=[C:2]([C:18]2[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=2[NH:25][C:26](=[O:31])[C:27]([CH3:29])([CH3:28])[CH3:30])[CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 122742,6-DibromopyridineHCID 516892Sodium BicarbonateHCID 19045057N-(2-borono-4-methylphenyl)-2,2-dimethylpropanamide

Product 1

HCID 19047053N-[2-(6-bromo-2-pyridinyl)-4-methylphenyl]-2,2-dimethylpropanamideYield 75.5%

Reagents, catalysts & solvents 3

HCID 84124Bis(triphenylphosphine)palladium chlorideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 24 g (0.1 mol) 2,6-dibromopyridine, 0.250 g palladium bis(triphenylphosphine) dichloride, and 40 mL dimethoxyethane was stirred under nitrogen for 20 min, after which 12 g (0.05 mol) N-(2-borono4-methylphenyl)-2,2-dimethylpropanamide and a solution of 26 g sodium bicarbonate in 300 mL water was added, and the mixture heated to reflux for 5 h. After cooling to 50° C., 50 mL ethyl acetate was added and stirred until it reached room temperature. The reaction mixture was diluted with 300 mL ethyl acetate and washed successively with water and brine. The organic extracts were dried over magnesium sulfate, filtered, and evaporated to dryness. The crude product was purified by chromatography on silica using 20:1 chlorobutane/ethyl acetate mixture as eluent to yield 13.1 g of the title compound as light tan crystals melting at 120°-126° C. 1H NMR (CDCl3): δ 1.28 (s,9H), 2.40 (s,3H), 7.30-8.4 (6H), 10.9 (s,1H,NH).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 5 h
  3. stirringstirred until it
  4. customreached room temperature
  5. washwashed successively with water and brine
  6. dry with materialThe organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe crude product was purified by chromatography on silica using 20:1 chlorobutane/ethyl acetate mixture as eluent

Sources & evidence

ORD record
ord-c1750b911b0648e18987d19da78c0eac
Source dataset
uspto-grants-1997_05
Patent number
US05631206

Reaction notes

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