Diisopropylamine → 1-(1,3-benzodioxol-5-yl)-2-(6-methyl-2-pyridinyl)Ethanone

HRID 1432419Notes

Reaction equation

HRID 1432419 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[N:13]1[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:20].CON(C)[C:24]([C:26]1[CH:34]=[CH:33][C:29]2[O:30][CH2:31][O:32][C:28]=2[CH:27]=1)=[O:25]>C1COCC1>[O:30]1[C:29]2[CH:33]=[CH:34][C:26]([C:24](=[O:25])[CH2:20][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]([CH3:19])[N:13]=3)=[CH:27][C:28]=2[O:32][CH2:31]1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 79372,6-LutidineHCID 10921728N-methoxy-N-methylbenzo[d][1,3]dioxole-5-carboxamideHCID 178418339Butyllithium

Product 1

HCID 688850001-(1,3-benzodioxol-5-yl)-2-(6-methyl-2-pyridinyl)EthanoneYield 87.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (2.5 M in hexanes, 13.8 mL, 34.4 mmol) was added slowly to a solution of diisopropylamine (4.53 mL, 32.3 mmol) in anhydrous THF (50 mL) at −78° C. After being stirred for 0.1 hour, the mixture was allowed to warm up to 0° C. Stirring continued for 0.5 hour. The mixture was then cooled to −78° C. and 2,6-lutidine (3.76 mL, 32.3 mmol) was added slowly. The mixture was allowed to warm up to 0° C. and stirred for 0.5 hour. The mixture was then cooled to −78° C. before the slow addition of benzo[1,3]dioxole-5-carboxylic acid methoxy-methyl-amide (4.5 g, 21.5 mmol; see Example 2 above) in anhydrous THF (10 mL). The mixture was stirred at −78° C. for 0.5 hour, at 0° C. for 0.5 hour, and at room temperature for 2 hours. The mixture was then quenched with ammonium chloride aqueous solution and extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate, filtered, and concentrated. After purification using column chromatography on silica gel (eluent: ethyl acetate (2): hexanes (8)), 4.8 g (87%) of 1-Benzo[1,3]dioxol-5-yl-2-(6-methyl-pyridin-2-yl)-ethanone as a yellow solid was obtained. MS (ESP+) m/z 256.1 (M+1). 1H NMR (400 MHz, Methanol-d4) δ 7.56 (t, 1H, J=7.5 Hz), 7.39 (dd, 1H, J=1.8 Hz, 8.3 Hz), 7.30 (dd, 1H, J=0.5 Hz, 1.8 Hz), 6.93 (m, 1H), 6.83 (m, 2H), 5.98 (s, 2H), 4.87 (s, 2H), 2.50 (s, 3H).

Workup

  1. stirringStirring
  2. waitcontinued for 0.5 hour
  3. temperatureThe mixture was then cooled to −78° C.
  4. temperatureto warm up to 0° C.
  5. stirringstirred for 0.5 hour
  6. stirringThe mixture was stirred at −78° C. for 0.5 hour, at 0° C. for 0.5 hour
  7. waitat room temperature for 2 hours
  8. customThe mixture was then quenched with ammonium chloride aqueous solution
  9. extractionextracted with ethyl acetate
  10. washThe extract was washed with brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customAfter purification

Sources & evidence

ORD record
ord-3822de4310ee4dafa5abcc6a6ba90806
Source dataset
uspto-grants-2009_11
Patent number
US07612094B2

Reaction notes

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