SU567408A3 - Method of cracking racemic pantolactone - Google Patents

Description

Methylpigan With pangoic acid in an almost pure crystalline form, if one or water-alcohol, in particular, water-methanol solutions of d, t sodium pantoate are mixed with {-) - 3-aminomethylpinel hydrochloride. At the same time, the desired d-pantolactone is obtained in a clean, crystalline form from mother liquor. The boiling point of (-) - and (+) 3 aminomethyl pinanes is low at 110 ° C at 20 mm prog. facilitates cleaning and recovery of the used optically active base. The racemic pantolactone interacts with an equivalent amount of alkali metal hydroxide, in particular sodium hydroxide, in an aqueous solution, with the formation of an alkali metal salt of racemic pantoic acid, and it is advisable to heat the aqueous solution of pantolactone to 50-100 ° C for 20 minutes “It is advisable to mix the solution of the alkali metal d, t salt of pantoic acid thus obtained with an equivalent amount of the acid additive salt of (-) - or (+) - 3 - aminomethylpinel. Moreover, it is recommended to work at temperatures from 0 to 90 ° C, preferably from 40 to 60 ° C.

B-salts of strong inorganic acids, hydrogen halides, in particular chlorides and bromides, are used as acid-additive salts. But you can also use nitrates, phosphates and salts of organic acids, in particular acetates. It is important to apply solutions containing from 5 to 40% by weight of pantolactone.

The acid addition salt is added in solid form or expediently in a solvent medium, preferably in water. Low solvents such as methanol or ethanol, acetone, nitriles, for example) acetoshiryl, amides of acids, for example dimethylformamide, in particular, in mixtures with water can also be used as solvents that are miscible with water. Generally, solutions containing from 5 to 25% by weight of an acid addition salt are used. When used as a solvent of an aqueous alcohol, the alcohol content may be up to 60% by weight, preferably from 30 to 50% by weight. Diastereomeric salts of d and B - pantoic acids and (-) - or (+). 3-aminomethylpine is obtained by exchange reaction. At the same time, the salt of d-pantoic acid (+) - 3 aminomethylpinel or E - pantoate (-) - 3 aminomethylpinean is hardly soluble, crystallizes out of solution and can be filtered from the easily soluble salt remaining in the mother liquor.

The filtered salt of d - pantoic acid (+) - 3 - aminomethyl. Thshiane or the salt of E-pangoic acid (-) - 3 - aminomethylpinan is dissolved or suspended in water and mixed by a usual method with a sufficient amount of alkali metal oxide, for example, sodium hydroxide. The purity of the filtered salt can be improved by allowing the crystallized solution to be suspended again in water, strongly sprinkled about 10 minutes, and then again

filter out. By extraction with an organic solvent, such as simple ether, or methylene chloride, (-) - or (+) - 3 - aminomethylpinan is recovered and recovered. After that, the aqueous phase, for lactonization, it is advisable to acidify with acid or sulfuric acid to a pH value of 1 and upon termination of lactonization, achieved by standing around the mixture for 2 hours at room temperature, d - (-) - pantolactone is extracted with such organic solvents as methylene chloride or ether.

A solution of the salt of C - pantoic acid (+) - 3 aminomethylpinan is treated with alkali, the residue is recovered- (+) - 3 - aminomethylpinan, and after oxidation, the E- (+) - nadtolactone is released.

E - (+) - pantolactone can be subjected to racemization in a known manner and the resulting racemate

it is possible, to return to the process, t - Natriypantoate can also be subjected to simple racemization directly in solution, without separation of E- (+) pantolactone.

From the solution of d - panthoate (-) - 3 - aminomethylpine it is possible to isolate the desired d - pantolactone and purify it. At first, at least an equivalent amount of a strong base is added, for example, sodium hydroxide, the separated (-) - 3 - aminomethylpinan is recovered by extraction

The organic solvent, for example, ether or benzene, and then the aqueous base solution is acidified with concentrated hydrochloric acid or sulfuric acid.

In this case, d - pantheum is first separated.

an acid that quickly turns into a cyclic d i-: (t-) -pantolactone compound and can be extracted from the aqueous salt solution using solvents such as methylene chloride or ether.

The crystalline E - panthoate of (-) - 3 - aminomethylpinan can be split into (-) - 3 - aminomethylpinan and E1 - pantolactone using an aqueous alkali using the analogous method, and both the (-) - 3 - aminomethylpinan residue and 8-pantolactone are obtained, which can be racemized by a known method and returned to the process.

The proposed splitting of the racemate (-) - or (+). 3 - amimethylene pco6einio is expediently implemented by mixing the alkali metal salt of d, - pantoic acid with only half of the equivalent amount of the acid addition salt of (-) - 3 - aminomethylpinel or (+) - 3 - aminomethineinan. At the same time, the hardly soluble diastereomeric - pantoate of (-) - 3 - aminomethylpinel or d pantoate of (+) - 3 - aminomethylpinel is isolated, and d - pantoic acid or - pantoic acid remains dissolved as an alkaline salt. With this method

it is advisable to work with the molar ratio

1: 0.5 to 0.7. After filtration, the resulting filtrate is acidified as described above and d (-) - or f- (+) - pantolactone is extracted from it by extraction with an organic solvent.

Concentrations are consistent with the above conditions.

The alkaline salt of pantoic acid remaining in the filtrate can, without transmuting into (+) pantolactone, immediately undergo racemization and be used again to split the racemate.

The remaining salt of d - pantoic acid (+) - 3

α-aminomethylpinel is broken down with alkali metal hydroxides, the separated (+) 3-aminomethylpine is extracted with organic solvents in an alkaline medium, and the aqueous phase is acidified.

When lactonization is completed, d - (-) is recovered.

-Pantolactone Organic Dissolver lt.

Optically active bases (+) and (-) - 3 - aminomethyl pinanes are stable at separate stages in the implementation of this method. None of the required reaction stages receive measurable amounts of by-products, which means that when recycling (+) - or (-) - 3 - aminomethylpinan and spantolactone, they do not require any purification of either 3 aminomethylpinan or racemized pantolactone for reuse. .

The optical purity of the d-pantolactone separated by the proposed method corresponds even after twenty-fold recirculation of the optically active base used, remaining each time of the racemized pantolactone, as well as the solvents used - within the analysis errors indicated in example 3 to the data obtained after the first separation, so no need for special cleaning operations.

The use of readily available, above-mentioned acid-additive sidly (+) - or (-) - 3 aminometipinan allows you to get optshshski pure (-) - pantolactone with a yield of up to 84%,. Example.

A, (t) - 3 - formylpinan. 500 ml (428 g) of (-) d - pinene with a specific rotation of the polarization plane of about -35.8 ° (pure 1 dm) and 250 mg of dimeric cyclooctadienyl - 1, 5 - rhodium chloride are fed into a high-pressure vessel with a capacity of 1 l. After displacing the air with a mixture of carbon monoxide and hydrogen in an equimolar ratio, the pressure is increased to 100 atm and then the reaction mixture is heated to 110 ° C, with an additional supply of the gas mixture under pressure for. 6 hours maintain a pressure of 650 atm. After cooling and lowering the pressure, a reaction mixture is obtained, which, according to the results of gas chromatography analysis, consists of 11 wt.% (-) - and gpinene, 61 wt.% Of optically active 3 - foopfflpine and 26 wt.% Of aldehyde, which represents structural index. Reakpiosguyu mixture

the catalyst is distilled off by molecular distillation under reduced pressure. The learner is subjected to fractional distillation in a column with 20 moving plates and reflux

the number 1: 5. At 103-104 ° C and 18 mm Hg. 285 g of (+) 3 - formilpinan are obtained with value a j + 19.17 ° (pure). The code for (-) - 3 - formyl pinan is 52% of theoretical, in terms of (-) - a - pinene.

B. (.-) - 3 - formylpinan. In the autoclave with

a mixer with electromagnetic control},

having a reaction volume of 10 liters, heated

3000 g (approx. 3.5 l) (+) - a - pinene with a value

(a i + 38.0 ° (pure) and 1 g of dimeric chloride

rhodium cyclooctadine - 1, 5 - yl (RhCICOD), / to 70 ° C and subjected to a reaction with a mixture of carbon monoxide and hydrogen in a volume ratio of 1: 1 at a pressure of 650 atm. The specified pressure podder live for 36 hours additional feed

gas mixture under pressure. At the end of the reaction, they are pressurized and pressurized in an autoclave. A reaction mixture is obtained, which, according to the results of analysis by gas chromatography, consists of 15.5% a - pinene, 1% / 3 pinene, 72.1% (-) - 3 - formyl pinan and 10.4% isomeric aldehydes. The reaction mixture was separated by fractional distillation. The resulting 1810 g of pure in structure (-) - 3 - formylpinan have a value of -23.1 ° (pure) and a boiling point of 77 ° C at 5 mm Hg. PRI me R 2.

A. (+) - 3-aminomethylpinan and (+) - 3 - aminomethylpinane hydrochloride.

2.5 liter pressure vessel

300 g of ethanol and 50 g of a skeletal cobalt catalyst (Rene cobalt) are fed and the air is removed by flushing with nitrogen. Then, 400 g of liquid ammonia and hydrogen are supplied under pressure to achieve a total pressure of 50 atm. Then the reactionary

the mixture is heated to 80 ° C and a pressure of 150 atm is created with the help of hydrogen. Within 6 hours, 200 g of (+) - 3 - formyl pinan is added in portions. After a further 2 hours, the reaction mixture is cooled and relieved. Receive 650 g

mix, from which by fractional distillation 106g of (+) - 3 - aminomethyl pinanan with a PO-111 ° C boiling point at 20 mm Hg is obtained. 120 g of the 3-aminomethylpinel obtained in this way is dissolved in 1.3 l of pentaa and,

Shiva, dry hydrogen chloride is introduced at a temperature of 0-5 ° C. When there is no more free amine in the mixture, the crystals formed are sucked off and dried. Obtain 142 g of hydrochloride (+) - 3 aminomethylphenane with a value of M + 35,4 ° (with:

 1, methanol), 118 g of hydrochloride (+) - 3-aminomethylpine, having a value (above M -f35.4 °, recrystallized from butyl acetate -ethanol. Obtain 85 g of shdrochloride (+) - 3 -aminomethylpine with the value of a - + 40.5 °. From

stock solution get this 29 g with a value

la 17.3 °. Salt with a value of + 40.5 ° will recrystallize once more from ethanol butyl acetate. Receive 70 g of hydrochloride (+) - 3 aminomethyl pinanan with a value of “li. + 44.3 °. If 30 g of hydrochloride (+) - 3 - aminomethylpinel with the value of all + 35.4 ° recrystallized .. are extracted three times from a mixture of ethyl acetate and methaulule, then hydrochloride (+) - 3 aminomethylpinel is obtained with a value of Wi ,7 4.7 °.

B, (-) - 3 - aminomethylphenol. In an autoclave with a stirrer, 150 g of a skeletal cobalt catalyst (Rene cobalt), suspension of another in 1000 ml of ethanol and 3.5 kg of ammonia, are heated to 80 ° C. Hydrogen is then pressurized until a total pressure of 150 bar is reached. 2020 g (-) - 3 formilpinan is pumped in for 6 hours. Additional supply of hydrogen under pressure is maintained at a constant pressure. After the reaction, the autoclave is allowed to cool and relieve pressure. The reaction yield (3450 g) is separated by fractional distillation. The resulting 1450 g of pure in structure (-) - 3 - amipomethylpinel with a boiling telocuricum of 100 ° C at 11 mm Hg. has a value of 32.6 °. (clean) .

Hydrochloride (-) - 3 - aminomethylpine. In a three-neck flask with a capacity of 1 l, 100 g of (-) - 3 - aminomethylpinel with M -32.6 ° (pure) is mixed with 100 ml of methanol and 500 ml of butyl acetate. At a temperature of about -5 ° C, dry, gaseous HCE is introduced into the liquid inside the flask. (-) - 3 - Aminomethylpinane hydrochloride precipitates. At the end of the precipitation, 25 ml of methanol are added, the mixture is heated under reflux for one hour and then cooled to 0 ° C. The precipitated crystals are removed, washed with 100 ml of cold butyl acetate and dried. 91 g of (-) - 3 - aminomethylpinel hydrochloride with a value of 23–44.0 ° (c 4; СНЗОН). By reaction with aqueous sodium hydroxide solution, extraction with ether and subsequent perionizing from hydrochloride, (-) - 3 - aminomethylpinan can be obtained with a value of fa -39.6 ° (pure). ..

EXAMPLE 3 To a solution of 10 parts of sodium hydroxide in 100 parts of water was added 32.5 parts of d, pantolactone. This mixture is then heated to 80 ° C for 30 minutes, and the racemic sodium salt of pantoic acid is formed. By feeding 2N hydrochloric acid solution, the pH of the resulting solution is adjusted to 8.5. A solution of 24.5 parts of (+) - 3-aminomethylpinan hydrochloride is introduced into the solution over a period of 10 min at room temperature; + 43.1 ° (c 1, methanol) in 150 parts of water, as a result of which the aggregate of crystals and mother liquor immediately outgrows as a thick mass. After stirring for 2 hours at room temperature, the suspension is cooled to 0 ° C, the totality of crystals and mother liquor is sucked off and washed twice with pebolk1m quantity of cold water. After the state of the crystals, 38.6 parts of the d-pantoic acid salt of (+) - 3-aminomethylpinan are half-dried; wcd98%; , ° 40.3 ° (s 1, methanol).

The resulting filtrate is alkalinized with dilute sodium hydroxide solution and removed by brief shaking with 50 parts of ether to remove unreacted (4) -3-aminomethyl-methyl residues.

E - pantoate sodium contained in the filtrate is regulated by acidifying the solution with half - concentrated sulfuric acid to a pH value of 1. After standing for 2 hours at room temperature, lactonization into E - (+) - pantolactone is completed. After you eat the salt salt 6

- (+) - pantolactone in the extractor for 12 hours, npocTbSM is continuously removed with ether from the aqueous phase. .

After ether hardening,%; 5 parts of (+) - pantolactone are obtained, yield 95%; a., + 38.0 ° (1% in water). ,

By recrystallization from 60 parts of diisopropyl ether, 13 parts of pure t- (+) -pantolactone are obtained with a yield of 80%, based on the racemic pantolactone used; of 48.9 ° (1% in water). The crystallized d-pantoic acid salt of (+) - 3 - aminomethylpipane is then suspended in 200 parts of water to 200 parts of ether and alkalinized with concentrated sodium hydroxide. The separated (+) - 3 -aminomethylpin is converted by strong shaking into the ether phase and, after separation of the aqueous phase, is recovered by evaporation of the ether. 19.5 parts of (+) - 3 - aminomethylpinel are obtained. (94% of the initial amount).

By dissolving in n-pentane and feeding hydrogen chloride, the amine is converted again to the hydrochloride; M 42.9 ° (1% in methanol), which can be used again for the resolution of the racemate. The ethereal solution of (+) - 3 aminomethylpyan is mixed in a simple manner with a stoichiometric amount of glacial acetic acid, as a result of which the acetic acid salt, which after filtration is immediately outweighed; M + 32 ° (1% in methanol) can be used again for the resolution of the racemate.

After separation of the ether phase, d pantolactone is obtained by immediately acidifying the aqueous phase with semi-concentrated sulfuric acid (pH 1) and after standing for 2 hours at room temperature and saturation with common salt in an extractor for 12 hours, is continuously extracted with ether.

 After evaporation of the ether, 15.3 parts of d (-) - pantolactone are obtained; 94%; -38.6 ° (1% in water). By recrystallization from 30 parts of dpiz (zpropyl ether, 13.1 parts of pure d - (-) -pantolactone are obtained with a total yield of 81%.)

2 o racemic pantolactone used; Q B -49,8 ° (1% in water). .

EXAMPLE 4 To a solution of 8 parts of sodium tdroxide in 80 parts of water, add 26 n: tolactone gels for 26 hours and heat to 20 ° C for 20 minutes. Adjust the pI of the solution with dilute hydrochloric acid to 8, 5 and then at room temperature for 10 minutes, stirring, a solution of 26.4 parts of the salt of acetic acid (+) - 3 - aminomethylpinan is added dropwise; ajl, 32 ° (1% in methanol) in 100 parts of water. After stirring for 2 hours, cooled to 0 ° C, the resulting precipitate is filtered and washed with a small amount of cold water. Get 29 parts of the salt of d-pangoic acid (+) - 3 amiamethylpinan 92%; and 1 - (1% in methanol). .

Phintral is acidified with concentrated sulfuric acid, and after standing for 1 hour 2 hours and after saturation with sodium chloride, E - (+) - pantolactone is extracted from the mixture in the extractor. After evaporation of the ali ether, 13.0 parts of - (+) pantolactone (100%) are obtained; a, 0 + 27.8 ° (1% in water).

Salt of d - pantoic acid () 3 - aminomethylpine is suspended in 00 parts of water and 200 parts of ether and alkalinized with sodium hydroxide. The ether phase is separated and (+) - 3 - aminomethyl-shan is recovered from it.

The aqueous phase is acidified with sulfuric acid, and d - (-) - pantolactone is extracted from the mixture after saturation by cooking with an extractor.

After evaporation of the ether, 12 parts of d (-) - pantolactone are obtained; 92%; 39.2 ° (1% in water). By recrystallization from 25 parts of diisopropyl ether, 9.7 parts of optically pure d - (-) - pantolactone are obtained with a total yield of 75%, calculated on the d, f-pantolactone used; "11 ° -50.2 ° (1% input)„

Example 5. To a solution of 1 part of sodium hydroxide in 50 parts of water, 3.25 parts of d are added, Pantolactone and the resulting mixture is heated to 80-90 ° C for 20 minutes.

The pH of the solution is adjusted to 8.5 and 5.05 parts of (+) - 3-aminomethylpinan hydrochloride are added in portions at room temperature; + 43 ° (1% in methanol). After 10 minutes, a precipitate formed, which was filtered and dried after standing for 10 hours at room temperature.

4.0 parts of d - pantoic acid (+) - 3 - aminomethylpinane are obtained; 100% a + 38.8 ° (1% in methanol).

The filtrate with the pantoic acid salt of (+) - 3 - aminomethylpinan dissolved in it is alkalinized with sodium hydroxide, and (+) - 3 - aminomethylpinan is recovered by 20 parts of ether. The aqueous phase is acidified with sulfuric acid and, after standing for one hour at room temperature, is extracted 5 times with methylene chloride, each time in 20 parts. After concentration of the combined chlorofoil extrusions, 1.25 parts of E- (+) - pantolactone are obtained;

 +30 (1% in water). The crystals of d - pantoic acid (+) - 3 - aminomethyl pygane salt are suspended in 20 parts of water and 20 parts of ether, and the resulting mixture is treated with sodium hydroxide solution. From the ether phase of the rivers, (+) - 3 aminomethylpinan are metered. The aqueous phase is acidified to

when complete, lactonisapdy is extracted five times.

methylene chloride flax, each time in 20 parts.

From condensed methylene chloride get

1, 4 4acTJi d - (-) pantolactone; 86%; all

-31 ° (We in water). After recrystallization from

mixtures of tert, butanol and petroleum ether

get d - (-) - pantolactop with a common output

62%; a -48, b (1% input).

Example 6. In the four-neck flask capacity

2 l, equipped with a stirrer, a thermometer, a cold inverse and a dropper with a capacity of 50 g ml, are dissolved 130 g (1 mol) d, -E pantolactone in 300 ml of water and heated to 80 ° C, K

100 g (1 mol) of 40% aqueous sodium hydroxide solution are added dropwise to this solution for 20 minutes and further stirred for 10 minutes at 80 ° C. If necessary, the pH value of this solution is adjusted to 8.8 by feeding

drops 1 n. solution of hydrochloric acid or 40% sodium hydroxide. This pH value corresponds to the pH value of a concentrated aqueous solution of sodium pantoate, which can be easily established by preliminary experience. Then within 2 minutes pour in the solution and;} 106 g (0.52 mol) of hydrochloride. (-) - 3 -; amine methycnan; -42.8 ° (1%, in methanol) in 450ml of water and obtained ciyrecb, the temperature of which contains at 50 °; C, stir additionally while slowly / until reaching room temperature. With

this P pantoate (-} - 3 - aminomethylpine

obtained as a collection of white crystals

and Uterine solution, which is sucked off on the suction and twice additionally rinsed with water, each time in an amount of 150 ml.

40% sodium hydroxide is added to the combined filters until a pH value of 13 is reached. Insignificant remnants of unreacted (-) - 3 - and shnomemetilpinap extract twice

methylene chloride, each time in the amount of 75 ml.

Concentrated sulfuric acid is then added to the filtrate until a pH of 1 is reached and evaporated in a rotary evaporator.

Claims (2)

apparatus in a vacuum obtained using a water-jet pump, before the onset of crystallization of inorganic salts. During this operation, d-pantoic acid, separated from d-pantoate of sodium, is converted into a cyclic compound d-pantolactone, which can be isolated by extraction with methylene chloride (2-150 ml, 3,100 ml). After distilling off methylene chloride, 66.8 g of d - (-) - pantolactone are obtained with a value of c, 42.3 (D, in water). After recrystallization from 85 ml of dshiropropyl ether, oh lactone gives 53.4 g (82% ) pure d (-) - pantolactone with a melting point of 91-92 ° C and a value of -51.6 ° (1% in water). Crystalline K pantoate () -3-aminomethyl; oxyhydrate is suspended in 200 ml of water and mixed with 40% aqueous and sodium alkalis until a pH value of 13 is reached. The separated (-) - 3-aminomethyl-pinan is separated first as the upper phase and after adding 150 ml methylene chloride can be extracted as a lower phase, the extractant is extracted twice more with methylene chloride, each time in an amount of 50 ml, the amino compound holding the solutions is combined, and solution of (-) - 3-aminomethylpinan in them is absorbed in an equivalent amount of 1N. hydrochloric acid solution (pH 5.4). The aqueous phase contains 102.8 g (97%) of (-) - 3 - aminomethylpinel hydrochloride used and, after adding 3.2 g of the cleavage reagent to it, can be immediately used to reintegrate the same amount of diastereomers. In a single-alkaline solution of B-sodium pantoate, concentrated sulfuric acid is mixed in until the pH value is 1. This mixture is kept at room temperature for one hour and then the pantolactone formed during this time is extracted with methylene chloride (2,150 ml, 3-100 ml) „ The chloromethylene phases are combined and the solvent is evaporated in a rotary evaporator. As the residue, 68.8 g of raw pantolactone is obtained with a value of + 43.6 ° (1% in water), which after heating for 2 hours to 133 ° C together with 56 g of 50% sodium hydroxide no longer rotate the flat ™ Paul Riza. This racemized product can be without further purification together with d, - pantolactone, obtained by recrystallization in diisopropyl ether from a mother liquor of 9 g; W -4 ° (1% in methanol) is used for the next separation of diastereomers after adding fresh d, f-pantolactone to it. The cleavage of racemic pantolactone with (-) - aminomethylpinan described in the same manner is repeated nine times. In this case, the optical purity of the crude d - (+) - pantolactone and (-) - 3 - aminomethylpinel hydrochloride returned to the process remains unchanged in the usual limits of brittleness. The losses of d, - pantolactone and hydrochloride of (-) - 3 - aminomethylpinel at each stage of separation averages 3.3 and 3.1%, respectively, and do not have an increasing trend. Example. In a four-necked flask with a capacity of 2 l, equipped with a stirrer, a reflux condenser, a thermometer and a 500 ml dropping funnel, in the manner described in Example 4, 130 g (1 mol) d, - pantolactone is converted into an aqueous solution of sodium pantoate with a pH value of 8.8. Then it is cooled to 50 ° C and a solution of 106.1 g (0.52 mol) of (-) 3 - aminomethylinane 43.3 ° (1% in methanol) in 450ml of 50% aqueous methanol is dropped in for approximately 2 minutes. After a few minutes, a white crystallized 6-pantoate of (-) - 3-aminomethyl-pinane is formed, which after one hundred hours, after 2 hours. Suck on the suction and twice additionally Yroshtayut water, each time in the amount of 150 ml. The filtrate and washed water are combined by adding 40% sodium hydroxide solution by dropping to a pH of 13 and removing twice with methylene chloride, each in a quantity of 75 ml. Chloromethylene extracts contain about 8 g of (-) - 3 - aminomethylpinane. The aqueous methanol solution is acidified with concentrated sulfuric acid to a pH value of 1 and in a rotary vacuum apparatus in vacuo, obtained by means of a water jet; evaporation until crystallization of inorganic salts. Separated from d-sodium pantoate, d-pantoic acid is converted under these conditions into a cyclic compound d - (-) - pantolactone, which is isolated by extraction with methylene chloride (2-150 ml, 3,100 ml). After distillation of methylene chloride, 64 are obtained , 9 g d - (-) - pantolactone with the value of "1 44.6 ° (1% in water). The crude lactone is dissolved by heating in 85 ml of diisopropyl ether. After infection, an insignificant amount of d - (-) - pantolactone is slowly cooled to + 10 ° C and thus 54.5 g (84%) of pure d - (-) - pantolactone are obtained with a value from 1 to 51.5 ° (1% in water). . The crystalline - (-) 3 - aminomethyl pinanate pantoate is further processed in the manner described in Example 4. Chloromethylene extracts of (-) - 3 - aminomethylpinan are combined and mixed with 1N. aqueous solution of hydrochloric acid until the pH of the aqueous phase is 5.4. This aqueous solution contains 101.7 g (96%) of the starting optically active base in the form of hydrochloride and can be used for the next racemate cleavage, without further purification, and after adding 4.3 g of fresh (-) - 3 - aminometalpin hydrochloride. Analogously to example 4, from a water-alkaline solution of E - pantoate 1tatri can be obtained 69.2 g of crude B- (+) - pantolactone +45.8 (in water), which, after heating for 2 hours to 133 ° C together with 56 g 50% aqueous sodium lye no longer rotates the polarization plane. A strongly alkaline solution of d, 8-sodium pantoate after adding 62 g of fresh d, E-pantolactone is heated to 80 ° C for 20 minutes, the pH value being adjusted to 8.9, and in this form can be re-used in the next section of your 2 diatheomers. The claims of the invention: 1. A method of splitting racemic pantolactone by the interaction of an alkali salt d, t, 3567408.4 - pantoic acid with optically active aminoadditive salt of (-) - 3 aminomethyl nasal and subsequent crystallization of the precursor (+) - 3 - aminomethylpinane In this case, diatheomeric salts, which are used in a molar ratio of 1: 0.5–0.7. the fact that, in order to improve the target code, the priority product and simplify the process, as an optical 5.01.01.74: the use of acid-additive Acid-active amine utilizes (+) -3-aminomethylpinan acid salt. -additive salts of (-) - 3 - aminomethylpinel or 09.11.74: the use of acid-additive (-n) - 3 aminomethylphenane. salts (-) - 3 aminomethylpinane. 2. The way pop. 1, which are attributed to the fact that during the examination: alkali salt of d, 6 - pantoic acid and acids-1. Patent GDR N 37505, cl. 12 g 24, 1970. Sources of information taken into account