Ethyl »-butylmalonate

Into a 2-litre, three-necked flask, fitted with a separatory funnel, a mechanical stirrer and a reflux condenser, place a hot solution of 200 g. of potassium hydroxide in 200 ml. of water. Stir the solution and add slowly 200 g. of ethyl n-butylmalonate (Section 111,154). A vigorous reaction occurs and the solution refluxes. When all the ester has been added, boil the solution gently for 2-3 hours, i.e., until hydrolysis is complete a test portion should dissolve completely in water. Dilute with 200 ml. of water and distil oflF 200 ml. of liquid in order to ensure the complete removal of the alcohol formed in the hydrolysis (1) it is best to connect the flask by means of a wide delivery tube to a condenser set for downward distillation (compare Fig. II, 41, 1 but with a mercury-sealed stirrer in the centre neck). Replace the separatory funnel and the reflux condenser. 

Sodium (9.6 parts) was dissolved in butanol (192 parts) and di-n-butyl ethyl 1 -methyl-n-butylmalonate (62,B parts) and urea (14.4 parts) were added to the warm solution with agitation. The mixture was then heated to reflux temperature in three quarters of an hour and maintained for 2 hours. The reaction mass was kept, water (150 parts) added, the aqueous portion separated, and the butanol layer extracted with water (3 x 50 parts). The combined aqueous extracts were then given 3 small extractions with benzene, the aqueous liquors separated, charcoaled,filtered and precipitated with concentrated hydrochloric acid (acid to congo-paper). The solid was collected, washed with water, dissolved in N-sodium hydroxide and reprecipitated with carbon dioxide. On recrystallization, from aqueous alcohol, the pentobarbitone was obtained. 

MIP2 84S152) and ethyl benzoylacetate in polyphosphoric acid at 100-110°C (79MIP2) gave 3-substituted l//-pyrimido[l,2-a]quinolin-l-ones (313, R = Me, Ph). Cyclocondensation of 2-(phenylamino)quinoline with benzyl(chloroformyl)ketene in xylene and with bis(2,4,6-trichlorophenyl) butylmalonate at 160°C for 3 h afforded anhydro-3-hydroxy-2-benzyl-4-phenyl-l-oxo-l//-pyrimido[l,2- ]quinolinium hydroxide (314) (79CB1585) and its 2-butyl derivative [91AP(324)863], respectively. 

A solution of 200 g. (3.57 moles) of potassium hydroxide (Note 1) in 200 cc. of water is placed in a 2-1. round-bottom flask fitted with a reflux condenser, a mechanical stirrer and a separatory funnel. The stirrer is started and to the hot solution 200 g. (0.92 mole) of ethyl sec.-butylmalonate (Note 2) is added slowly. The solution refluxes gently due to the heat of saponification. After all of the sec.-butylmalonic ester has been added, the solution is refluxed gently for two hours. The solution is diluted with 200 cc. of water and 200 cc. of liquid is then distilled from the solution. This is done in order to remove all of the alcohol formed during the saponification (Note 3). 

The ethyl sec,-butylmalonate was prepared from sec-butyl bromide and malonic ester according to the general method described in Org. Syn. 4, n. The yield of ester boiling at i24-i32°/28 mm. was 80-81 per cent of the theoretical amount. The yields of 3-methyl pentanoic acid given in this procedure were obtained with this grade of ester. 

Other adds may be prepared by this general procedure thus w-caproic add may be obtained from ethyl w-butylmalonate in 75 per cent yield. 

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