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

Participants

Role	Name	HCID	Charge
Reactant	4-Chlorobenzylamine	HCID 66036	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	1-(tert-Butoxycarbonyl)-4-((tert-butoxycarbonyl)amino)piperidine-4-carboxylic acid	HCID 1268225	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Dichloromethane	HCID 6344	—
Product	4-Tert-butoxycarbonylamino-4-(4-chloro-benzylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester	HCID 45139444	86.4%

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09006430B2
Source dataset	uspto-grants-2015_04
ORD ID	ord-3f57d812326647f2be381e49b8552502
Source note	uspto-grants-2015_04