Réaction #44872

Équation de réaction

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

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

triethylamine

triphosgene

NaHCO3

→

oil

Rendement 62.0%

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

Rendement 62.0%

Solvants

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   TempératureThe reaction mixture was refluxed for 19 hours
2. 2
   TempératureThe reaction mixture was refluxed for another 24 hours
3. 3
   TempératureThen cooled
4. 4
   Extractionextracted with ethyl acetate 100 ml for three times
5. 5
   ExtractionThe combined extract
6. 6
   Lavagewas washed with brine
7. 7
   Séchagedried over MgSO4
8. 8
   Concentrationconcentrated

Mode opératoire

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.

Source