Diisopropylamine → 2-(3'-Dimethylaminobenzoylmethyl)nicotinic acid N-methylamide

HRID 1065284Notes

Reaction equation

HRID 1065284 reaction equation
C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.C([N-]C(C)C)(C)C.[Li+].[CH3:27][NH:28][C:29](=[O:37])[C:30]1[CH:35]=[CH:34][CH:33]=[N:32][C:31]=1[CH3:36].[CH3:38][N:39]([CH3:51])[C:40]1[CH:41]=[C:42]([CH:48]=[CH:49][CH:50]=1)[C:43](OCC)=[O:44]>O1CCCC1>[CH3:27][NH:28][C:29](=[O:37])[C:30]1[CH:35]=[CH:34][CH:33]=[N:32][C:31]=1[CH2:36][C:43](=[O:44])[C:42]1[CH:48]=[CH:49][CH:50]=[C:40]([N:39]([CH3:38])[CH3:51])[CH:41]=1

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 2724682Lithium diisopropylamideHCID 12833322N,2-Dimethyl-3-pyridinecarboxamide2×HCID 12833325Ethyl 3-(dimethylamino)benzoateHCID 178418339Butyllithium

Product 1

HCID 128333262-(3'-Dimethylaminobenzoylmethyl)nicotinic acid N-methylamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

263 ml. of 1.6 M.n-butyl lithium in hexane (420 mmol.) were slowly added to a solution of 58.7 ml. (420 mmol.) of diisopropylamine in 200 ml. of dry tetrahydrofuran stirred at -10° C. under nitrogen. To the resulting solution of lithium diisopropylamide, a solution of 30 g. (200 mmol.) of 2-methylnicotinic acid N-methylamide (Compound XII) in 200 ml. of dry tetrahydrofuran was slowly added at -20°--30° C. The resulting red reaction mixture was stirred under nitrogen at -20°--30° C. for an additional two hours. Then, a solution of 38.6 g. (200 mmol.) of ethyl 3-dimethylaminobenzoate in 100 ml. of dry tetrahydrofuran was slowly added at -20°--30° C. with stirring under nitrogen. Stirring under nitrogen was continued for 1 hour at the same temperature. The reaction mixture was then quenched with 250 ml. of saturated sodium chloride solution and extracted three times with ethyl acetate. The ethyl acetate phases were combined, washed four times with water, once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and evaporated at reduced pressure to a thick oil (55.6 g.) which was dissolved in a small amount of isopropanol and chromatographed on silica gel using 5% isopropanol/chloroform as the eluant. The last major fraction to be eluted (approx. 24 g.) was rechromatographed on silic gel using 2% isopropanol/chloroform as the eluant. The largest fraction contained the crude product (17.2 g.).

Workup

  1. stirringwith stirring under nitrogen
  2. stirringStirring under nitrogen
  3. waitwas continued for 1 hour at the same temperature
  4. customThe reaction mixture was then quenched with 250 ml
  5. extractionof saturated sodium chloride solution and extracted three times with ethyl acetate
  6. washwashed four times with water
  7. dry with materialonce with saturated sodium chloride solution, dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated at reduced pressure to a thick oil (55.6 g.) which
  10. dissolutionwas dissolved in a small amount of isopropanol
  11. customchromatographed on silica gel using 5% isopropanol/chloroform as the eluant
  12. washThe last major fraction to be eluted (approx. 24 g.)
  13. customwas rechromatographed on silic gel

Sources & evidence

ORD record
ord-bf25a9ad470a4118959db73ea5b62926
Source dataset
uspto-grants-1982_05
Patent number
US04329349

Reaction notes

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