β-Methylene-D,L-asparagine

Article abstract of DOI:10.1021/jo00206a032

The synthesis of β-methylene-D,L-asparagine (I) was carried out as follows. 2-Bromopropionitrile was condensed with the anion of di-tert-butyl malonate yielding tert-butyl 3-cyano-2((tert-butyloxy)carbonyl)butyrate (II).Formation of the anion of II with sodium hydride followed by reaction with bromine yielded tert-butyl 3-cyano-2-bromo-2-((tert-butyloxy)carbonyl)butyrate (III).Elimination of hydrogen bromide was effected by gently heating III with potassium carbonate in pyridine.The product was a 90:10 mixture of tert-butyl 3-cyano-2-((tert-butyloxy)carbonyl)but-2-enoate (V) and tert-butyl 3-cyano-2-((tert-butyloxy)carbonyl)but-3-enoate (IV).Isomer V is readily converted to IV by reaction with sodium hydride followed by quenching with hydrochloric acid.Treatment of the mixture of IV and V with sodium hydride followed by reaction with chloramine yielded tert-butyl 3-cyano-2-amino-2-((tert-butyloxy)carbonyl)but-3-enoate (VI).The latter was hydrolyzed to the desired β-methylene-D,L-asparagine (I) by heating at 40 deg C for 12 h with 20percent hydrochloric acid.Acetylation of I with acetic anhydride yielded N-acetyl-β-methylene-D,L-asparagine (VIII).