Diethyl s-butylmalonate

Note. (1) Diethyl s-butylmalonate, b.p. 110-120 °C/20 mmHg, is prepared by reacting 2-bromobutane with diethyl malonate. Use the general procedure described for the butyl isomer (Expt 5.133) but extend the period of heating under reflux to 48 hours to complete the alkylation. 

Synthesis. Dn-Isoleucine is synthesized in about 27% over-all yield by the method of Marvel (554). Diethyl sec.-butylmalonate (A) is prepared in 83% yield from diethyl malonate, sodium, absolute ethanol and sec.-butyl bromide (b.p. 91.3°C.) essentially by the method of Romburgb (673). a-Bromo- S-methylvaleric acid (B) is pr ared in about 67% yield by the alkaline hydrolysis of (A), isolation of sec.-butylmalonic acid ((j), and bromination and decarboxylation of (C). DL-Isoleucine (D), prepared by amination of (B), is recrystallized from 30% ethanol. It has been suggested (39, 485) that the product should be repeated recrystallized from 80% ethanol to free it from allo-isoleucine. It has been found in the writers laboratory that recrystallization from 20% ethanol is an effective purification procedure. The described s thesis is essentially that originated by Brasch and Friedman (125) and Ehrlich (237) and employed by Abd halden and Zeisset (39). 

Diethyl n-butylmalonate, benzyl bromide, and LiCl in hexamethylphosphoramide heated 1.5 hrs. at 155° product. Y 71%. F. e., also dialkylation, s. M. Asaoka, K. Miyake, and H. Takei, Chem. Lett. 1975, 1149. 

Hydroxypyridone ring synthesis. 80 g. phenothiazine, diethyl n-butylmalonate, and unglazed clay plate fragments heated 22 hrs. at 277° crude l-keto-2-n-butyl-3-hydroxy-lH-pyrido[3,2,l-kl]phenothiazine. Y 73%.—Clay plate catalyzes this reaction and particularly prevents decreasing yields of larger batches. F. e., also with phenoxazine, s. M. Harfenist et al., J. Org. Chem. 27, 3977 (1962). 

Bromine added dropwise with stirring at 0° to diethyl allyl-n-butylmalonate, and stirring continued 30 min. at 0° a-n-butyl-a-carbethoxy-<5-bromo-y-valerolactone. Y 92.8%. F. e. s. M. de Moura Gampos, B. 93, 1075 (1960). 

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