Dimethylamine → HCID 19600150, compound

HRID 611364Notes

Reaction equation

HRID 611364 reaction equation
Cl.[O:2]1[C:6]2[CH2:7][NH:8][CH2:9][CH2:10][C:5]=2[CH:4]=[CH:3]1.[C:11]1([CH:17]2[CH2:19][CH:18]2[C:20]2[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][CH:21]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH2:29]([N:31]([CH2:34]C)[CH2:32]C)C.C(P(=O)(OCC)OCC)#N.CNC.C=O>CN(C)C=O.O>[CH3:29][N:31]([CH2:34][C:3]1[O:2][C:6]2[CH2:7][N:8]([C:24](=[O:25])[C:23]3[CH:27]=[CH:28][C:20]([CH:18]4[CH2:19][CH:17]4[C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)=[CH:21][CH:22]=3)[CH2:9][CH2:10][C:5]=2[CH:4]=1)[CH3:32]

Participants

9

Reactant 6

HCID 674DimethylamineHCID 712FormaldehydeHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 195999074,5,6,7-Tetrahydrofuro[2,3-c]pyridine hydrochlorideHCID 19600226HCID 19600226, compound

Product 1

HCID 19600150HCID 19600150, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[2,3-c]pyridine hydrochloride, 0.237 g (1.0 mmol) of 4-(2-phenylcyclopropyl)benzoic acid and 0.55 ml (4.0 mmol) of triethylamine in 30 ml of N,N-dimethylformamide, 0.245 g (1.5 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. 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 90 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. extractionfollowed by 2 extractions with ethyl acetate
  3. washThe combined organic layer was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. dissolutionThe resulting crude product was dissolved in 10 ml of acetic acid
  7. stirringby stirring at 100° C. for 90 minutes
  8. distillationAfter the solvent was distilled off under reduced pressure
  9. extractionextracted with ethyl acetate 2 times
  10. washThe combined organic layer was washed with water
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThe resulting crude product was purified by silica gel column chromatography (ethyl acetate/methanol=5/1)

Sources & evidence

ORD record
ord-735c3cffc1f74690b31218ca3e0185fb
Source dataset
uspto-grants-1999_12
Patent number
US05998433

Reaction notes

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