Dimethylamine → (E)-N,N-dimethyl-[5-(2,3-diphenylpropenoyl)-4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-ylmethyl]amine

HRID 611345

Reaction equation

HRID 611345 reaction equation
Cl.[O:2]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[CH:4]=[CH:3]1.[C:11]1(/[C:17](=[CH:21]\[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)/[C:18](O)=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH2:28]([N:30]([CH2:33]C)[CH2:31]C)C.C(P(=O)(OCC)OCC)#N.CNC.C=O>ClCCl>[CH3:28][N:30]([CH2:33][C:3]1[O:2][C:10]2[CH2:9][CH2:8][N:7]([C:18](=[O:19])/[C:17](/[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:21]/[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:6][C:5]=2[CH:4]=1)[CH3:31]

Participants

8

Reactant 6

HCID 674DimethylamineHCID 712FormaldehydeHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 700620alpha-Phenylcinnamic acid, (E)-HCID 195999414,5,6,7-Tetrahydrofuro[3,2-c]pyridine hydrochloride

Product 1

HCID 19600147(E)-N,N-dimethyl-[5-(2,3-diphenylpropenoyl)-4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-ylmethyl]amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine hydrochloride, 0.247 g (1.1 mmol) of (E)-2,3-diphenylpropenoic acid and 0.5 ml (4.0 mmol) of triethylamine in 30 ml of dichloromethane, 0.245 g (1.5 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. After the solvent was distilled off, water was added, followed by 2 extractions with ethyl acetate. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was dissolved in 10 ml of acetic acid; 0.135 ml (1.50 mmol) of 50% aqueous dimethylamine and 0.122 ml (1.50 mmol) of 37% aqueous formaldehyde were added, followed by stirring at 100° C. for 120 minutes. After the solvent was distilled off under reduced pressure, the residual solution was alkalified with 5% aqueous sodium hydrogen carbonate and extracted with ethyl acetate 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (ethyl acetate/methanol=5/1) to yield the desired product.

Workup

  1. temperaturecooling
  2. distillationAfter the solvent was distilled off
  3. additionwater was added
  4. extractionfollowed by 2 extractions with ethyl acetate
  5. washThe combined organic layer was washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. dissolutionThe resulting crude product was dissolved in 10 ml of acetic acid
  9. stirringby stirring at 100° C. for 120 minutes
  10. distillationAfter the solvent was distilled off under reduced pressure
  11. extractionextracted with ethyl acetate 2 times
  12. washThe combined organic layer was washed with water
  13. dry with materialdried over anhydrous sodium sulfate
  14. distillationthe solvent was distilled off under reduced pressure
  15. customThe resulting crude product was purified by silica gel column chromatography (ethyl acetate/methanol=5/1)

Sources & evidence

ORD record
ord-66c8c2ac4fc148ffa5ac045ccbe6feca
Source dataset
uspto-grants-1999_12
Patent number
US05998433

Linked notes

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