Homoserine lactone hydrobromide → 2-Amino-4-bromobutanoic acid hydrobromide

Participants

Reaction Steps

This compound is prepared by a modification of the procedure used by Nollet, Huting and Pandit to prepare tertiary butyl 2-(N-carbobenzyloxy)amino-4-bromobutyrate. (Tetrahedron, 25, 5971 (1969) ##STR11## To 3.64 g (20.0 mmoles) of 2-aminobutyrolactone hydrobromide is added 182 ml of glacial acetic in a 500 ml three-necked flask equipped with a fritted glass gas bubbler, calcium chloride drying tube, and magnetic stirrer. Hydrogen bromide gas is then vigorously bubbled into the resultant suspension while stirring at ambient temperature. After three hours, all of the starting material has gone into solution and hydrogen bromide addition is discontinued. The reaction mixture is stirred at ambient temperature overnight and then is concentrated to dryness at reduced pressure yielding 5.2 g of crude 2-amino-4-bromobutyric acid hydrobromide as a white solid. This crude acid is dissolved in 25 mls absolute methanol after which hydrogen bromide gas is bubbled in for one minute. Monitoring reaction progress by NMR (BrCH2 -:CH3 -O-integration) indicates negligible reaction after stirring overnight at room temperature. After refluxing for 72 hours the reaction is judged to be complete. The reaction mixture is then concentrated to dryness at reduced pressure yielding crude methyl 2-amino-4-bromobutyrate hydrobromide as a colorless oil. To a solution of this crude ester in 25 ml water is added 3.70 g (44.0 mmoles) of sodium bicarbonate while stirring vigorously in an ice bath. Immediately, 3.8 mls (4.1 g; 24 mmoles) of benzylchloroformate is added dropwise over ca. two minutes. After ten minutes, the ice bath is removed, allowing the reaction mixture to warm to room temperature over 30 minutes. It is then poured into a separatory funnel and extracted with ether (3×25 ml), the combined portions of which are washed with saturated sodium bicarbonate (3×25 ml), dried over magnesium sulfate and concentrated, yielding 5.44 g of an oily white solid. Recrystallization from hexane-ether yields 1.96 g of methyl-2-(N-carbobenzyloxy)-amino-4-bromo-butyrate (A) as white clusters having mp 87°-9°. This represents a 30% overall yield from 2-amino-butyrolactone hydrobromide. Tlc (Silica Gel F-254; CHCl3) shows one spot having Rf =0.15.

Provenance & Evidence