Sodium Hydroxide → (S)-benzyl 4-(2-(tert-butoxycarbonylamino)-4-(methylthio)butanamido)piperidine-1-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Sodium Hydroxide	HCID 14798	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Boc-L-methionine	HCID 89857	—
Reactant	Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 2733084	—
Reactant	4-Amino-1-N-Cbz-piperidine	HCID 17846640	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(S)-benzyl 4-(2-(tert-butoxycarbonylamino)-4-(methylthio)butanamido)piperidine-1-carboxylate	HCID 86688073	100%

Reaction Steps

A solution of HBTU (8.1 g, 21 mmol), (S)-2-(tert-butoxycarbonylamino)-4-(methylthio)butanoic acid (5.3 g, 21 mmol) and DIEA (8.2 mL, 47 mmol) in DMF (50 mL) was stirred at ambient temperature for 30 minutes. Benzyl 4-aminopiperidine-1-carboxylate (5.0 g, 21 mmol) was added and the mixture was stirred at ambient temperature for 18 hours. The mixture was poured into 1N NaOH (500 mL) and the combined organic layers were extracted into EtOAc (500 mL). The combined organic layers were washed with 1N HCl (500 mL) and brine (500 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to yield (S)-benzyl 4-(2-(tert-butoxycarbonylamino)-4-(methylthio)butanamido)piperidine-1-carboxylate (10 g, 21 mmol, 100%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08754226B2
Source dataset	uspto-grants-2014_06
ORD ID	ord-03464b571e664c12a611bb3abc3d4c73
Source note	uspto-grants-2014_06