Absorbable a-Cyanoacrylate Compositions

Polymerizable 3-(2-cyano-acryloyloxy)-butyric acid ethyl ester has been prepared in a two-step process using 3-hydroxybutyrate and cyanoacetic acid followed by treatment with formaldehyde. This and related alkyl ester cx-cyanoacrylate monomers are useful as tissue adhesives/sealants in surgical and related medical applications. 

Preparation of 3-(2-Cyano-Acetoxy)-Butyric Acid Ethyl Ester 

A reactor was charged with ethyl-3-hydroxybutyrate (194.0 g), cyanoacetic acid (149.83 g), 4-dimethylaminopyridine (10.76 g), and 1500 ml of CH2CI2 and then treated with 75 ml of DMF. The solution was chilled in an ice-water bath and treated with dicyclohexylcarbodiimide (363.45 g) dissolved in 600ml of CH2CI2. A white precipitate formed within five minutes after the start of the addition, and the mixture was stirred overnight. The precipitate was then removed by filtration and the filtrate concentrated. The product was isolated in 73% yield after being distilled twice under vacuum, bp= 100-109°C/0.20-0.27mmHg. 

A very small amount of this monomer product was placed between two moist fingertips and bonded the fingertips strongly within one minute. 

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