Diisopropylethylamine → (S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester

https://huagongshe.com/reaction/1182091

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate	HCID 2733207	—
Reactant	(3S)-4-(benzyloxy)-3-(((tert-butoxy)carbonyl)amino)-4-oxobutanoic acid	HCID 7017887	—
Reactant	3-(4-Chlorophenoxy)azetidine hydrochloride	HCID 57350197	—
Solvent	Dichloromethane	HCID 6344	—
Product	(S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester	HCID 69409254	—

Reaction Steps

A solution of (S)-2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester (5.0 g, 13.99 mmol) in dichloromethane (50 ml) is treated with diisopropylethylamine (7.51 ml, 41.97 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (4.49 g, 13.99 mmol). To the reaction mixture is added 3-(4-chloro-phenoxy)-azetidine hydrochloride (3.06 g, 13.99 mmol) and stirring continued for 3 hours. The dichloromethane is evaporated and residue partitioned between ethylacetate and saturated NaHCO3 solution. The ethylacetate phase is washed with 1M HCl solution and brine, dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 1:1 ethylacetate/hexane) to afford (S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester. [M-BOC] 389.0.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07288537B2
Source dataset	uspto-grants-2007_10
ORD ID	ord-f72b4ddbd7a84ad3ab562d391c52cf9c
Source note	uspto-grants-2007_10