Pyridine → N-(2-phenylethyl)cyclopropanamine

HRID 561814Notes

Reaction equation

HRID 561814 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.N1C=CC=CC=1.[C:11]1([CH2:17][C:18](Cl)=O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>ClCCl.C1COCC1>[C:11]1([CH2:17][CH2:18][NH:4][CH:1]2[CH2:3][CH2:2]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 7679Phenylacetyl chlorideHCID 69828Cyclopropylamine

Product 1

HCID 10844712N-(2-phenylethyl)cyclopropanamine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of cyclopropanamine (1 eq.) in dichloromethane (0.13 M) was added sequentially at 0° C. pyridine (1.5 eq.) and phenylacetyl chloride (9 eq.). The resulting mixture was slowly warmed to RT and stirred at RT for 3 h. After quenching with 1 N aq. HCl, the reaction mixture was extracted with EtOAc. The combined organic extracts were washed with sat. aq. NaHCO3 and brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. The crude amide thus obtained was taken up in THF (0.3 M) and added BH3.SMe2 complex (3 eq.). The reaction was heated to reflux and the volatiles were slowly distilled off. The resulting distillation residue was carefully quenched with 1 N aq. HCl and allowed to stir at 50° C. overnight. The reaction was cooled to 0° C. and the pH of the solution was brought to ˜12 with 1 N aq. NaOH before it was extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. The crude product thus obtained could be further purified by way of column chromatography (SiO2, 2:1 (v/v) Hex:EtOAc→EtOAc) afforded the title compound as a colorless oil.

Workup

  1. customAfter quenching with 1 N aq. HCl
  2. extractionthe reaction mixture was extracted with EtOAc
  3. washThe combined organic extracts were washed with sat. aq. NaHCO3 and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe crude amide thus obtained
  8. additionadded BH3
  9. temperatureThe reaction was heated
  10. temperatureto reflux
  11. distillationthe volatiles were slowly distilled off
  12. distillationThe resulting distillation residue
  13. customwas carefully quenched with 1 N aq. HCl
  14. stirringto stir at 50° C. overnight
  15. temperatureThe reaction was cooled to 0° C.
  16. extractionwas extracted with ether
  17. washThe combined organic extracts were washed with brine
  18. dry with materialdried over MgSO4
  19. filtrationfiltered
  20. concentrationthe filtrate concentrated in vacuo
  21. customThe crude product thus obtained could
  22. custombe further purified by way of column chromatography (SiO2, 2:1 (v/v) Hex:EtOAc→EtOAc)

Sources & evidence

ORD record
ord-87a1392f71f04fe7af81d3abc91c85e2
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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