4-Chlorobenzylamine → 4-Tert-butoxycarbonylamino-4-(4-chloro-benzylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester

Dry DMF (1 mL) was added to a mixture of 4-tert-butoxycarbonylamino-piperidine-1,4-dicarboxylic acid mono tert-butyl ester (151 mg, 0.44 mmol) and HATU (220 mg, 0.58 mmol) under nitrogen. N-Ethyldiisopropylamine (0.38 mL, 2.1 mmol) was added to the solution and the reaction mixture was stirred for 15 min. 4-Chlorobenzylamine (70 uL, 0.57 mmol) was added and the solution was stirred for 23 h at rt and under nitrogen. The reaction mixture was partioned between dichloromethane (10 mL) and water (10 mL). The aqueous phase was further extracted with dichloromethane (20 mL). The combined organic layers were dried (Mg2SO4), filtered and concentrated. Flash column chromatography on silica, eluting with 4% methanol in dichloromethane, gave 4-tert-butoxycarbonylamino-4-(4-chloro-benzylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (177 mg, 0.38 mmol, 86%). LC-MS (LCT2) m/z 490 [M+Na+], Rt 8.09 min.

1. stirringthe solution was stirred for 23 h at rt and under nitrogen
2. extractionThe aqueous phase was further extracted with dichloromethane (20 mL)
3. dry with materialThe combined organic layers were dried (Mg2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. washFlash column chromatography on silica, eluting with 4% methanol in dichloromethane

ORDレコード

ord-3f57d812326647f2be381e49b8552502

出典データセット

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09006430B2