反应详情

Sodium hydride (60%, 0.27 g, 6.7 mmol) is added to a solution of 4-benzyloxycarbonyl-2-oxo-piperazine (1.58 g, 6.7 mmol) in dry DMF (40 mL). After 30 minutes 4-bromomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.87 g, 6.7 mmol) is added and the reaction is allowed to stir for 16 h. The solvent is removed in vacuo and the residue is dissolved in ether and washed with NH4Cl. The aqueous phase is back-extracted with ether and the combined ether fractions are washed with water and brine to provide 4-(1-tert-butoxycarbonyl-piperidin-4-ylmethyl)-3-oxo-piperazine-1-carboxylic acid benzyl ester which is used without further purification. 1H NMR (300 MHz, CDCl3) δ 7.36 (s, 5H), 5.16 (d, 2H), 4.16 (s, 2H), 4.13 (br, 2H), 3.73-3.69 (m, 2H), 3.44-3.30 (m, 6H), 2.68 (bt, 2H), 1.85-1.73 (m, 1H), 1.58 (bd, 2H), 1.46 (s, 9H), 1.25-1.10 (m, 2H); MS (ion spray) 432 (M+H)+.

1. customThe solvent is removed in vacuo
2. dissolutionthe residue is dissolved in ether
3. washwashed with NH4Cl
4. extractionThe aqueous phase is back-extracted with ether
5. washthe combined ether fractions are washed with water and brine