反应详情

tert-Butyl 4-(1,2-dihydro-2-oxo-5-phenylimidazol-3-yl)piperidine-1-carboxylate was synthesised as described in J. Med. Chem., 2005, 48, 5921. A solution of 2-bromo-1-phenylethanone (5 g, 25 mmol) in DCM (10 ml) was added dropwise to a stirred solution of tert-butyl 4-aminopiperidine-1-carboxylate (6 g, 30 mmol) and DiPEA (9.84 ml, 57.5 ml) in DCM (50 ml) over 1 hour, the reaction mixture was then stirred at room temperature for 16 hours. Sodium cyanate (3.41 g, 52.5 mmol) was added, the reaction mixture was then cooled to 0° C., the pH was brought to pH 4 with acetic acid and the reaction mixtures was stirred from 0° C. to RT over 16 hours. The reaction mixture was poured into water and extracted with DCM (3×). Organics combined, washed with water (3×), brine, dried (MgSO4) and evaporated to dryness. The residue was triturated with ether, filtered and the solid was washed with ether to give a pale yellow solid (4.04 g, 47%). LC/MS (10% to 99%): M/Z (M+H)+ (obs)=344; tR=3.01.

1. temperaturethe reaction mixture was then cooled to 0° C.
2. customthe reaction mixtures
3. stirringwas stirred from 0° C. to RT over 16 hours
4. extractionextracted with DCM (3×)
5. washwashed with water (3×), brine
6. dry with materialdried (MgSO4)
7. customevaporated to dryness
8. customThe residue was triturated with ether
9. filtrationfiltered
10. washthe solid was washed with ether