Hydrochloric Acid → tert-Butyl 3-(4-oxo-4H-pyrrolo[3,4-d]thiazol-5(6H)-yl)azetidine-1-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Triethylamine	HCID 8471	—
Reactant	1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide	HCID 15908	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Lithium hydroxide, monohydrate	HCID 168937	—
Reactant	Methyl 5-(((1-(tert-butoxycarbonyl)azetidin-3-yl)amino)methyl)thiazole-4-carboxylate	HCID 66601525	—
Catalyst	4-(Dimethylamino)pyridine	HCID 14284	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	tert-Butyl 3-(4-oxo-4H-pyrrolo[3,4-d]thiazol-5(6H)-yl)azetidine-1-carboxylate	HCID 66601519	63.9%

Reaction Steps

A mixture of compound 3c (320 mg, 0.98 mmol) and LiOH.H2O (123 mg, 2.93 mmol) in THF (8 mL) and H2O (4 mL) was stirred at room temperature for 20 h. The pH of the reaction mixture was adjusted to 5 with aq. 10% HCl. Concentration gave the crude compound 3d. A mixture of compound 3d (0.98 mmol), HOBt (132 mg, 0.98 mmol), Et3N (0.41 mL, 2.93 mmol), EDCI (318 mg, 1.66 mmol), and DMAP (25 mg, 0.21 mmol) in DMF (4 mL) was heated at 65° C. for 5 h. The reaction mixture was cooled to room temperature and diluted with CH2Cl2. The solution was washed with H2O, dried over Na2SO4 and concentrated. Purification by flash column chromatography (silica gel, 3% MeOH/CH2Cl2) gave compound 3e (185 mg).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08759533B2
Source dataset	uspto-grants-2014_06
ORD ID	ord-b114df54a22148dd8f3bca1b8edc38fd
Source note	uspto-grants-2014_06