| 摘要 |
Prodn. of (E)-2-propyl-2-pentenoic acid of formula (I) comprises: (a) heating a 2-bromo-2-propyl-pentanoate ester of formula (II) in a polar aprotic amide solvent, opt. contg. H2O in the presence of a basic agent (III) to form a mixt. of (E)- and (Z)-2-propyl-2-pentenoate esters of formula (IV); and (b) saponifying (IV) with an alkali metal hydroxide in an aq. medium, opt. contg. an alcohol ROH, and acidifying the reaction mixt. with a strong acid to obtain (I). In the formulae, R = 1-4C alkyl. (III) comprises: (i) a sec. amine, (ii) a sec. or tert. amine and a weak inorganic base, (iii) an alkali metal carbonate, or (iv) an alkali metal carbonate and an alkali metal halide. (I) is described in Arch. Pharm., 310(4), 394(1977) and J.A.C.S., 93(17), 4242(1971). The solvent is DMF, N,N-dimethylacetamide or N-methylpyrrolidone. The sec. amine is piperidine or piperazine. The tert. amine is NMe3, NEt3, trimethyl-ethylenediamine or 1,4- diazabicyclo(2,2,2)octane. The weak inorganic base is an alkali metal carbonate or alkaline earth metal hydroxide. The alkali metal halide is a chloride or bromide. (III) esp. comprises piperazine and K2CO3. The (III):(II) molar ratio is 0.5-3:1. Step (a) is effected at 30-130 (esp. 70-80) deg.C. Saponification is effected with 1-10 equiv. of NaOH at reflux temp. in an aq. medium contg. 50-150 vol.% ROH, esp. where R = Et. The reaction mixt. is acidified with HCl at -10 to +20 deg.C. Saponification is limited to 90-92% conversion, and unsaponified ester is extracted with a water-immiscible solvent before acidifying the aq. phase. USE/ADVANTAGE - (I) is an anti-epileptic agent. The process gives higher yields (65-80%) than prior art processes (cf. EP 293753) and gives (I) with high purity (at least 98%).
|
