1-Hydroxybenzotriazole → N-Methoxy-N-methyl-3-isobutylcyclobutanecarboxamide

https://huagongshe.com/reaction/1912044

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Methanamine, N-methoxy-, hydrochloride (1:1)	HCID 81138	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	cis-3-Isobutylcyclobutane carboxylic acid	HCID 83635449	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Triethylamine	HCID 8471	—
Product	N-Methoxy-N-methyl-3-isobutylcyclobutanecarboxamide	HCID 86675032	109.4%

Reaction Steps

3-Isobutylcyclobutanecarboxylic acid (62.7 g) and DMF (500 mL) were mixed. To the mixture were added N,O-dimethylhydroxylamine hydrochloride (46.9 g), triethylamine (83.9 mL), HOBt.H2O (73.8 g) and WSC.HCl (92.3 g). The resulting mixture was stirred at RT overnight. To the reaction mixture was added water (500 mL). The mixture was extracted with ethyl acetate/hexane=1/1 (250 mL×2). The combined organic layer was washed with water (250 mL), aqueous 10 w/v % sodium carbonate (250 mL), water (250 mL), 1 N hydrochloric acid (500 mL), water, saturated aqueous sodium bicarbonate (250 mL) and then brine (250 mL). The organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo to give the title compound (87.5 g) as a crude product.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08604069B2
Source dataset	uspto-grants-2013_12
ORD ID	ord-d8cba523520a4d41a691f7031283b5f2
Source note	uspto-grants-2013_12