ETHYL 1-AMINO-1-CYCLOBUTANECARBOXYLATE &

Uses

1-Aminocyclobutanecarboxylate hydrochloride is a carboxylic acid ester compound that can be used as a pharmaceutical intermediate.

Synthesis

Sodium azide (3.14 g, 48.3 mmol) was partially dissolved in dry DMSO (50 mL) under nitrogen atmosphere at room temperature. ethyl 1-bromocyclobutanecarboxylate (3.91 mL, 24.2 mmol, Aldrich) was then added via syringe. The mixture was heated at 40 C for 7 h to obtain a homogeneous solution, cooled to room temperature with continuous stirring overnight. The reaction mixture was then poured into water (700 mL) and ether (200 mL) was added. The ether layer was washed three times with half the concentration of brine and once more with brine. The organic layer was dried with sodium sulfate, filtered and distilled under reduced pressure to give ethyl 1-azido cyclobutanecarboxylate (4.00 g) as a clarified oil.

Ethyl 1-azido cyclobutanecarboxylate (4.00 g, 23.6 mmol) was dissolved in methanol (150 mL) under nitrogen atmosphere. Palladium carbon (840 mg, 10% wt/wt) was then added and hydrogen was passed through to remove the nitrogen. the reaction was judged to be complete after 3 hr (LCMS). The reaction mixture was filtered through diatomaceous earth, which was washed with methanol. The combined methanol solutions were made acidic by the addition of HCl (2.0 M in ether) and the solvent was then removed under reduced pressure. The 1-aminocyclobutanecarboxylic acid ethyl ester hydrochloride (4.70 g) obtained then slowly solidified to a low melting point waxy solid containing a considerable amount of methanol as determined by proton NMR.