CH383380A - Process for the preparation of new basic esters of 2,6-dialkylbenzoic acids - Google Patents

Description

  

  Process for the preparation of new basic esters of 2,6-dialkylbenzoic acids It has been found that new basic esters of 2,6-dialkylbenzoic acids of the general formula I (see formula sheet), in which R1, R2 and R3 are identical or different lower alkyl groups and n and m are 1 or 2, can be achieved by adding a 2,6-dialkylbenzoyl halide of the general formula II, in which X is halogen and R1 and R. are as defined above,

   with an amino alcohol of the general formula III, in which R ″, n and m have the above meanings, or with its salt reacts with HX.



  The process is carried out, for example, that an acid halide of the formula 1I prepared by generally known methods, for example an acid chloride, with a hydrohalic acid salt of an amino alcohol of the formula 11I, for example a chlorohydrate, to a higher temperature, preferably 100-200 , heated. In this case, hydrogen halide is split off in a spontaneous reaction and a crude melt of the ester hydrohalide is obtained.

   But you can also genids after the well-known reaction of the reaction of the acid halide with the free amino alcohol, optionally in an inert solvent, such as. B. chloro form, ether, aromat. Hydrocarbons, processes to arrive at the desired product.



  The crude hydrohalides of the 2,6-dialkylbenzoic acid alkylamino esters shown in the above manner are purified by known methods. They can be converted into the free bases by reaction with alkali hydroxides or carbonates.



  The esters of general formula I have a local anesthetic effect and are used in therapy in the form of their salts or in the form of their quaternary compounds. In the following examples, all temperatures are given in degrees Celsius. The melting points are not corrected.



  <I> Formula sheet </I>
EMI0001.0045
    <I> Example 1 </I> o, o'-Dimethylbenzoic acid 2- (N-methyl-pyrrolidyl-2 ') - ethyl ester A mixture of 8.85 g, o'-dimethylbenzoyl chloride (bp. 85-87 111 Torr) and 8.47 g of 2- (N-methyl-pyrrolidyl 2 ') -ethanol chlorohydrate are heated in an oil bath while stirring.

   The strongly exothermic elimination of hydrochloric acid begins at an internal temperature of around 140 and the reaction temperature rises to 170. With the oil bath temperature constant, it is heated for another 15 minutes. The highly viscous product obtained is converted into the free base and this is fractionated. The o, o'-dimethylbenzo (N-methyl-pyrrolidyl-2 ') - ethyl ester boils at 112010.04 Torr.



       Fumarate: 4.4 g of the base obtained above, 1.96 g of fumaric acid and 5 cm3 of abs. Alcohol is heated until the components dissolve, mixed with 50 cm3 of ethyl acetate and allowed to crystallize. The analytically pure salt melts at 115-115.5.



  <I> Example 2 </I> o, o'-Dimethylbenzoic acid-2- (N-methyl-piperidyl-2 ') -ethyl ester chlorohydrate A mixture of 8.65 go, o'-dimethylbenzoyl chloride and 7.16 g 2- (N-methyl-piperidyl-2 ') - ethanol chlorohydrate are heated in an oil bath while stirring. At an internal temperature of 130 a stormy elimination of HCl begins, after which it is heated to around 145 internal temperature for a further 20 minutes.

   After the reaction mixture has cooled down, it solidifies into a glassy, brittle mass that is dissolved in 180 cm3 of acetone and treated with a little Norit. The crystalline hydrochloride of o, o'-dimethylbenzoic acid 2 - (N-methyl-piperidyl-2 ') ethyl ester is obtained from the solution. Crystallized again from acetone, the compound melts at 137-138.

 

Claims (1)

PATENT CLAIM Process for the preparation of new basic esters of 2,6-dialkylbenzoic acids of the general formula EMI0002.0030 wherein R1, R2 and R3 are identical or different lower alkyl groups and n and m are 1 or 2, characterized in that one is a 2,6-dialkylbenzoyl halide of the general formula EMI0002.0036 wherein X stands for halogen with an amino alcohol of the general formula EMI0002.0038 or reacts with its salt with HX.