تفاعل #44872

معادلة التفاعل

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

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

triethylamine

triphosgene

NaHCO3

→

oil

المردود 62.0%

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

المردود 62.0%

المذيبات

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was refluxed for 19 hours
2. 2
   درجة الحرارةThe reaction mixture was refluxed for another 24 hours
3. 3
   درجة الحرارةThen cooled
4. 4
   استخلاصextracted with ethyl acetate 100 ml for three times
5. 5
   استخلاصThe combined extract
6. 6
   غسيلwas washed with brine
7. 7
   تجفيفdried over MgSO4
8. 8
   تركيزconcentrated

الإجراء التجريبي

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.

المصدر