Reacción #44872

Ecuación de reacción

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

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

triethylamine

triphosgene

NaHCO3

→

oil

Rendimiento 62.0%

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

Rendimiento 62.0%

Disolventes

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was refluxed for 19 hours
2. 2
   TemperaturaThe reaction mixture was refluxed for another 24 hours
3. 3
   TemperaturaThen cooled
4. 4
   Extracciónextracted with ethyl acetate 100 ml for three times
5. 5
   ExtracciónThe combined extract
6. 6
   Lavadowas washed with brine
7. 7
   Secadodried over MgSO4
8. 8
   Concentraciónconcentrated

Procedimiento

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.

Fuente