반응 #44872

반응 방정식

tert-butyl 4-(aminomethyl)piperidine-1-carboxylate

1-isopropyl-1,3-dihydro-2H-benzimidazol-2one

triethylamine

triphosgene

NaHCO3

→

oil

수율 62.0%

tert-Butyl 4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H -benzimidazol-1-yl)carbonyl]amino}methyl)piperidine-1-carboxylate

수율 62.0%

용매

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   온도The reaction mixture was refluxed for 19 hours
2. 2
   온도The reaction mixture was refluxed for another 24 hours
3. 3
   온도Then cooled
4. 4
   추출extracted with ethyl acetate 100 ml for three times
5. 5
   추출The combined extract
6. 6
   세척was washed with brine
7. 7
   건조dried over MgSO4
8. 8
   농축concentrated

실험 절차

To a stirred solution of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2one (J. Med. Chem. 1999, 42, 2870-2880) (3.00 g, 17.02 mmol) and triethylamine (7.12 ml, 51.06 mmol) in 70 ml tetrahydrofuran was added triphosgene (5.15 g, 17.02 mmol) in 14 ml tetrahydrofuran at room temperature. The reaction mixture was refluxed for 19 hours. The mixture was then cooled to room temperature, tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (J. Prugh, L. A. Birchenough and M. S. Egbertson, Synth. Commun., 1992, 22, 2357-60) (3.28 g, 15.32 mmol) in 10 ml tetrahydrofuran was added. The reaction mixture was refluxed for another 24 hours. Then cooled and basified with aqueous saturated NaHCO3 50 ml, and extracted with ethyl acetate 100 ml for three times. The combined extract was washed with brine, dried over MgSO4 and concentrated. Flash chromatography of the residue (elutent: hexane/ethyl acetate=5/1 to 1/2) afforded a colorless oil 3.99 g (62%) as the titled compound.

출처