RU2621347C1 - Method of obtaining 1-alkyl-2-alkylcarbamoyl glycerine - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a process for the preparation of 1-alkyl-2-alkylcarbamoylglycerols of general formula I

where R₁ - hydrocarbon residue C16-C18, R₂ - methyl, ethyl, which can be used for medicamental therapy of arterial hypertension. The method consists in reacting the starting 1-alkylglycerols of general formula II

with trimethylchlorosilane in the presence of a base in a solvent medium. The reaction of the starting 1-alkylglycerols with trimethylchlorosilane is carried out in the presence of pyridine, and methylene chloride is used as the solvent. The reaction is carried out in an air atmosphere at 0°C with further addition of the corresponding alkyl isocyanate and subsequent treatment with a mixture of methanol-chloroform.

EFFECT: new method allows to increase the yield.

1 dwg, 1 tbl, 4 ex

Description

The invention relates to the field of medicine and the pharmaceutical industry and relates to methods for producing 1-alkyl-2-alkylcarbamoylglycerols, which can be used for drug therapy of arterial hypertension.

It is known that an agent based on 1-alkyl-2-alkylcarbamoylglycerol (ACG), which is a structural analogue of the precursor of platelet activation factor (FAT), a phospholipid, having the structure according to the formula: 1-O-alkyl-2-acetyl-sn-glycero-3 -phosphocholine, causes a long-term decrease in blood pressure (BP) in rats with spontaneous genetic and renovascular hypertension [Malekin SI Long-term normalization of blood pressure in SHR and 1-kidney 1-clip rats by synthetic precursor of stable PAF analogue without systemic effects in normotensive rats / S.I. Malekin, S.V. Kotelevtsev, S.A. Gavrilova et al // Pathophysiology. - 2011 .-- 18 (2). - P. 151-157].

Various glycerol derivatives were used as starting substrates for the synthesis of 1-O-alkyl-2-acetyl-sn-glycerophospholipids. So, 1-O-alkyl-2-O-acetyl-sn-glycerols were obtained from D-mannitol in 8 stages, which included 1,2-O-isopropylidine-sn-glycerol as a key intermediate in the synthesis scheme [Chacko G.K. Chemical synthesis of i-O- (D) -and 3-O- (L) -glyceryl monoethers, diethers and derivatives: glycerides, monoester phospholipids and diether phospholipids / Chacko G.K., Hanahan D.J. // Biochim. Biophys. Acta. - 1968. - 164. - P.252]. 1-O-alkyl-2-O-benzylglycerophosphocholine was prepared from 1,3-benzylidenglycerol and 1-deoxy-1-iodo-3-O-alkylglycerol. Naturally occurring O-alkyl glycerols have also been used as starting materials for the synthesis of alkyl phospholipids with a limited number of alkyl chains at the sn-1 and sn-3 positions.

Known synthesis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholines - analogues of platelet activation factor in 4 stages from epichlorohydrin. At the first stage, epichlorohydrin is esterified with various alcohols (tetradecyl, hexadecyl, octadecyl) to obtain glycidyl ethers (yield 78-80%). At the second stage, the epoxide cycle is opened with acetic anhydride to obtain acetylated products (yield 76-78%). The key step is the technique using a 1,3-specific lipase to produce 1-O-alkyl-2-acetylglycerol (yield 45-50%). Hydrolyzed products were phosphorylated to give 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (yield 80-85%) [Vijeeta T. Chemo enzymatic synthesis of rac 1 About alkyl 2 acetyl sn glycero 3 phosphocholine and its component / Vijeeta T., Balakrishna M, Karuna MSL, Rao BWSK, Prasad RBN // J Oleo Sci. - 2014 .-- 63 (9). - P.933-938].

When conducting screening studies, it was found that a number of structural homologs of the FAT precursor are promising for the development of antihypertensive drugs based on them. ACG was selected from the obtained candidates [patent RU 2414453 C2, published on 08/10/2010] and a detailed study of its effect on rat BP was carried out. It was shown that ACG causes a long-term decrease in blood pressure in rats with spontaneous genetic and renovascular hypertension, while the duration of the hypotensive effect of ACG upon its single administration was higher than that of currently widely used drugs, including calcium antagonists, diuretics, and angiotensin-converting inhibitors enzyme.

Several methods are known for preparing alkylcarbamoylglycerols.

In 1988, Surles JR et al. Used to obtain 1-O-hexadecyl-2-0- (methylcarbamoyl) glycerol method proposed by S. M. Gupta. and Bali A., allowing you to attach methylcarbamate fragment. The flask was purged with nitrogen before starting the reaction. To a solution of 1-O-hexadecyl-3-O-tritylglycerol (9.0 g, 16 mmol) and 4- (dimethylamino) pyridine (2.07 g, 17 mmol) in CH ₂ Cl ₂ (50 ml) was added methyl isocyanate (4.85 g, 85 mmol). The vessel in which the reaction took place was purged with N ₂ and sealed. The contents were kept in a nitrogen atmosphere with constant stirring in the dark at room temperature for 72 hours, after which the volatile components of the reaction were removed. 15.2 g of crude product was obtained, which was chromatographed on silica gel. Next, the trityl protection was removed from the obtained product (weighing 10.1 g) and re-purified by chromatography. The yield of (1-O-hexadecyl-2-O- (methylcarbamoyl) glycerol) was 62% [Surles JR Synthesis and Evidence for the Stability of a Glycerophosp hochloridate: rac -1-O-Hexadecyl-2-O- (methylcarbamyl) -sn -glycero-3-phosphoroc hloridocholine / JR Surles, MH Marx, C. Piantadosi. // J. Org. Chem. 1988, Vol. 53. P. 901-904 // J. Org. Chem. 1988, Vol. 53. P. 901-904].

Patents of Takeda Chemical Industries, Ltd., (Japan) - are devoted to the synthesis of glycerol derivatives. US Pat. No. 4,576,933 (A) [published March 18, 1986] describes the preparation of glycerol derivatives having antihypertensive activity. Among others, the preparation of 2-alkylcarbomoylglycerols -2- (N, N-dimethylcarbamoyl) -3-octadecylglycerol (1) and 2- (N, N-dibutyrylcarbamoyl) -3-octadecylglycerol (2) is described by the following methods:

1) preparation of 2- (N, N-dimethylcarbamoyl) -3-octadecylglycerol: (2- (N, N-dimethylcarbamoyl) -3-octadecyl-1-tritylglycerol (2.92 mg, 4.43 mmol) was added to 29 ml 80% acetic acid and the resulting mixture was stirred at 100 ° C. for one hour and then concentrated to dryness under reduced pressure.The residue was purified by silica gel column chromatography (13 g) using n-hexane-ethyl acetate (4: 1) 1.6 g of product was obtained (86.9% reaction yield).

2) 2- (N, N-dibutylcarbamoyl) -3-octadecylglycerol: 2- (N, N-dibutylcarbamoyl) -1-octadecyl-3-triglycerol (2.7 g) was dissolved in 30 ml of 80% acetic acid, and the solution stirred at 103 ° C. for 1.5 hours and concentrated to dryness under reduced pressure, the residue was purified on a silica gel column using n-hexane-ethyl acetate (4: 1) as an eluent. The product yield was 1.70 g (92.5%).

EP 0685457 B1 [published December 15, 1999] by the Japanese company Nippon Shinyaku Company, Limited describes methods for preparing glycerol derivatives (1,3-O-dioleoyl-2-O- (2-bromoethyl) carbomolyglycerol) from 1,3-O- dioleyl glycerol dissolved in pyridine, to which 120 mg (0.740 mmol) of N, N'-carbonyldimidazole was added and the mixture was kept at ambient temperature for 3 hours. After removal of the solvent, the residue was dissolved in methylene chloride, washed with a 5% aqueous solution of dihydrogen phosphate sodium, dried and concentrated. The residue was dissolved in N, N-dimethylformamide and 2-aminoethanol was added, the mixture was allowed to stand overnight. After completion of the reaction, the solvent was removed and the residue was dissolved in methylene chloride, washed with 5% sodium dihydrogen phosphate solution, dried, concentrated. The residue was passed through a chromatographic column. Depending on the derivative obtained, the yield of the substance was from 80 to 100%.

Closest to the proposed is a method for producing 1-alkyl-carbomoylglycerols described in patent RU 2414453 C2 [published on 08/10/2010], according to which, the starting 1-alkyl-glycerols are reacted with trimethylchlorosilane in the presence of triethylamine in toluene at -20 ÷ 0 ° C, then with an alkyl isocyanate and subsequent treatment of the reaction mixture with ammonium bifluoride in methanol at room temperature.

As the starting 1-alkylglycerols, compounds of the general formula are used

where R1 is the hydrocarbon radical - (CH ₂ ) _n CH ₃ (n = 10-18).

Obtaining 1-hexadecyl-2-methylcarbamoyl-glycerol.

To a solution of 3.67 g (0.012 mol) of 1-hexadecylglycerol and 1.17 g (0.012 mol) of triethylamine in 150 ml of toluene in an argon atmosphere at -20 ÷ 0 ° С was added a solution of 1.26 g (0.012 mol) of trimethylchlorosilane in 20 ml of toluene. The reaction mixture was kept at 0 ° C, 2 ml of methyl isocyanate was added and left overnight. Then it is filtered, the solvent is removed in vacuo, the residue is dissolved in 40 ml of hexane, 0.66 g (0.012 mol) of ammonium bifluoride in 40 ml of methanol are added, and they are kept at room temperature for 4 hours. The mixture was filtered through a layer of alumina, the solvent was removed in vacuo, 150 ml of hexane were added, filtered, hexane was removed in vacuo to give 3.33 g (77%) of 1-hexadecyl-2-methylcarbamoyl-glycerol, m.p. 59 ° C, R _f = 0.3 (silica gel, ether-hexane = 4: 1).

The disadvantages of the method are the low yield of 1-alkyl-2-alkylcarbamoylglycerols - 65-85%, the use of toxic triethylamine, low component loading, which makes it difficult to obtain a large amount of the compound for preclinical and clinical trials.

A new technical result of the invention is to increase the yield of the target product, to develop a method for producing the target product in large quantities, and to expand the arsenal of methods for producing drugs that can be used for drug therapy of hypertension.

To achieve a technical result in a method for producing 1-alkyl-2-alkylcarbamoylglycerols of the general formula I

where R ₁ is the hydrocarbon residue C16-C18; R ₂ is methyl, ethyl, which consists in the fact that the initial 1-alkylglycerols of the general formula II are reacted

with trimethylchlorosilane in the presence of a base in a solvent medium, characterized in that the starting 1-alkylglycerols are reacted with trimethylchlorosilane in the presence of pyridine, and methylene chloride is used as a solvent, and the reaction is carried out in an atmosphere of air at 0 ° C with the addition of the corresponding alkyl isocyanate and subsequent treatment with a mixture of methanol-chloroform.

The reaction scheme is shown in FIG. one.

The proposed method for producing 1-alkyl-2-alkylcarbamoyl-glycerols allowed to increase the yield of the target product to 98% and the purity of the target product to 98.9%.

New in the proposed method is that less toxic pyridine is used as the base instead of triethylamine, methylene chloride is used as the solvent. The reaction is carried out at room temperature in an atmosphere of air. In the proposed method does not require a hydrolysis step with a methanol solution of ammonium bifluoride.

As a result of the synthesis, 1-alkyl-2-alkylcarbamoylglycerols are obtained with a yield of up to 98% and a purity of 98.9%.

The mode of the new method for producing 1-alkyl-2-alkylcarbamoyl-glycerols was based on the results of experimental studies.

A new method for the preparation of 1-alkyl-2-alkylcarbamoyl-glycerols for a specialist does not explicitly follow from the prior art and a description of the method for producing 1-alkyl-2-alkylcarbamoyl-glycerols having an identical set of essential features was not found by the authors in the patent and medical literature . The proposed method is tested in laboratory conditions. Thus, the proposed technical solution meets the criteria of the invention, namely, "novelty", "inventive step" and "industrial applicability".

The method is as follows:

Example 1. Obtaining 1-hexadecyl-2-methylcarbamoylglycerol. To a solution of 21.6 g (0.068 mol) of 1-hexadecylglycerol and 9.9 ml (0.123 mol) of pyridine in 150 ml of methylene chloride, a solution of 7.4 g (0.068 mol) of trimethylchlorosilane in 20 ml of methylene chloride is added. The reaction mixture was kept at 0 ° C, 11.4 ml (0.1845 mol) of methyl isocyanate were added and left overnight. Then it is filtered, the solvent is removed in vacuo, the residue is dissolved in 200 ml of a 5% solution of methanol in chloroform, 50 ml of water are added and the mixture is shaken vigorously for one hour. Then the organic layer is separated on a separatory funnel. Then, a mixture of chloroform: benzene was added to the separated organic layer, and the solvent was removed in vacuo. The residue is dissolved in a volume of chloroform sufficient for complete dissolution and filtered through a layer of silica, which is then washed with a mixture of ethyl ether: chloroform: acetonitrile. The filtrate was dried in vacuo. 24.96 g (98%) of 1-hexadecyl-2-methylcarbamoylglycerol are obtained, mp. 59 ° C, R _f = 0.3 (silica gel, ether-hexane = 4: 1). ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm): 0.9 (3H, t, - С Н ₃ ), 1.2 (28 Н, m, -C H ₂ -), 1-6 (2Н, m, -OC H ₂ ); 2.8 (3H, s, -CONHCH ₃ ), 3.0 (1H, m, -OH), 3.4-3.6 (4H, m, - ¹ CH ₂ CH- ³ CH ₃ ); 3.8 (1H, s, -CONH-); 4.9 (1H, m, - ² CH-OCO-). IR spectrum (ν _max , cm -1): 1700 (СО); 3300 (NH, OH). Found,%: C 67.12; H 11.45; N, 2.94. C ₂₁ H ₄₃ NO ₄ . Calculated,% 67.52; H, 11.60; N, 3.75; Oh, 17.13 Quantitative content: 99.7%.

Example 2. Obtaining 1-hexadecyl-2-ethylcarbamoylglycerol. To a solution of 21.6 g (0.068 mol) of 1-hexadecylglycerol and 9.9 ml (0.123 mol) of pyridine in 150 ml of methylene chloride, a solution of 7.4 g (0.068 mol) of trimethylchlorosilane in 20 ml of methylene chloride is added. The reaction mixture was kept at 0 ° C, 14.6 ml (0.1845 mol) of ethyl isocyanate were added and left overnight. Then it is filtered, the solvent is removed in vacuo, the residue is dissolved in 200 ml of a 5% solution of methanol in chloroform, 50 ml of water are added and the mixture is shaken vigorously for one hour. Then the organic layer is separated on a separatory funnel. Then, a chloroform: benzene mixture was added to the separated organic layer, and the solvent was removed in vacuo. The residue is dissolved in a volume of chloroform sufficient for complete dissolution and filtered through a layer of silica, which is then washed with a mixture of ethyl ether: chloroform: acetonitrile. The filtrate was dried in vacuo. 25.65 g (yield 97%) of 1-hexadecyl-2-ethylcarbamoylglycerol are obtained. Mp 50 ° C, R _f = 0.34 (silica gel, ether-hexane = 4: 1). ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm): 0.9 (3H, t, - C H ₃ ); 1.2 (28 N, m, -C H ₂ ); 1.6 (2H, m, -OS H ₂ ); 2.4 (3H, s, -CONHC H ₃ ); 3.4-3.6 (4H, m, ¹ C H ₂ CH _- ³ C H ₂ ); 5.2 (1H, m, - ² CH-OCO-). Found,%: C 67.91; H 10.82; N 3.24. C ₂₂ H ₄₅ NO ₄ . Calculated,%: C 68.21; H, 11.62; N, 3.62. Quantitative content: 98.9%.

Example 3. Obtaining 1-octadecyl-2-methylcarbamoylglycerol. To a solution of 23.5 g (0.068 mol) of 1-octadecylglycerol and 9.9 ml (0.123 mol) of pyridine in 150 ml of methylene chloride, a solution of 7.4 g (0.068 mol) of trimethylchlorosilane in 20 ml of methylene chloride is added. The reaction mixture was kept at 0 ° C, 11.4 ml (0.1845 mol) of methyl isocyanate were added and left overnight. Then it is filtered, the solvent is removed in vacuo, the residue is dissolved in 200 ml of a 5% solution of methanol in chloroform, 50 ml of water are added and the mixture is shaken vigorously for one hour. Then the organic layer is separated on a separatory funnel. Then, a chloroform: benzene mixture was added to the separated organic layer, and the solvent was removed in vacuo. The residue is dissolved in a volume of chloroform sufficient for complete dissolution and filtered through a layer of silica, which is then washed with a mixture of ethyl ether: chloroform: acetonitrile. The filtrate was dried in vacuo. 26.31 g (96% yield) of 1-octadecyl-2-methylcarbamoylglycerol are obtained. Quantitative content: 99.3%. Mp 46 ° C, R _f = 0.42 (silica gel, ether-petroleum ether = 3: 1). ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm): 0.9 (3H, t, -C H ₃ ); 1-2 (30 N, m, -C H ₂ ); 1-6 (2H, m, -OCH ₂ ); 2.8 (3H, s, -CONHC H ₃ ); 3.0 (1H, m, -O H ); 3.4-3.6 (4H, m, - ¹ С H ₂ СН- ³ C H ₂ -); 3.8 (1H, s, -CON H -); 4.9 (1H, m, - ² C H- OCO-). Found,%: C 67.81; H 11.21; N 3.10. C ₂₂ H ₄₅ NO ₄ . Calculated,%: C 68.21, H 11.62, N 3.62.

Example 4. Obtaining 1-octadecyl-2-ethylcarbamoylglycerol. To a solution of 23.5 g (0.068 mol) of 1-octadecylglycerol and 9.9 ml (0.123 mol) of pyridine in 150 ml of methylene chloride, a solution of 7.4 g (0.068 mol) of trimethylchlorosilane in 20 ml of methylene chloride is added. The reaction mixture was kept at 0 ° C, 14.6 ml (0.1845 mol) of ethyl isocyanate were added and left overnight. Then it is filtered, the solvent is removed in vacuo, the residue is dissolved in 200 ml of a 5% solution of methanol in chloroform, 50 ml of water are added and the mixture is shaken vigorously for one hour. Then the organic layer is separated on a separatory funnel. Then, a chloroform: benzene mixture was added to the separated organic layer, and the solvent was removed in vacuo. The residue is dissolved in a volume of chloroform sufficient for complete dissolution and filtered through a layer of silica, which is then washed with a mixture of ethyl ether: chloroform: acetonitrile. The filtrate was dried in vacuo. 27.80 g (98% yield) of 1-octadecyl-2-ethylcarbamoylglycerol are obtained. Mp 42 ° C, R _f = 0.44 (silica gel, ether-petroleum ether = 3: 1). ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm): 0.9 (3H, t, - C H ₃ ); 1.2 (30 N, m, - C H ₂ -); 1.6 (2H, m, - OC H ₂ ); 2.4 (3H, s, - CONHC H ₂ CH ₃ ); 3.4-3.6 (4H, m, - ¹ C H ₂ C H - ³ C H ₂ -); 5.2 (1H, m, - ² С Н- ОСО-). Found,%: C 68.11; H 11.11; N, 3.30. C ₂₃ H ₄₇ NO ₄ . Calculated,%: C 68.82, H 11.72, N 3.49. Quantitative content: 99.1%.

Quantification and determination of impurities

Chromatographic system Dionex Ultimate 3000 (“Teppert”, Germany), including the following components: pump LPG-3400SD (or similar); WPS-3000SL autosampler (rthi similar); Thermostat TCC-3000SD (or equivalent); OAE detector) -3000 (or similar).

4,6×250 mm (или аналогичная).Hypersyl ODS C18 Chromatography Column, 5 μm 120

4.6 × 250 mm (or similar).

The flow rate of the eluent is 1 ml / min; sample volume 20 μl; column thermostat temperature 30 ° С; detection wavelength 200 nm.

The column is equilibrated with the mobile phase until a stable baseline is reached within 30 minutes. The standard solution and the test solution are subsequently analyzed.

Verification of suitability of the chromatographic system

The chromatographic system is considered suitable if the chromatogram of a standard solution of 1-O-alkyl-2-O-alkylcarbomoylglycerol:

- the retention coefficient of 1-O-alkyl-2-O-alkylcarbomoylglycerol is not less than 1.00;

- column efficiency calculated by the peak of 1-O-alkyl-2-O-alkylcarbomoylglycerol - not less than 5000 theoretical plates;

- the relative standard deviation of the retention times and peak areas of 1-O-alkyl-2-O-alkylcarbomoylglycerol calculated from 5 consecutive chromatograms does not exceed 2%;

the coefficient of asymmetry of the peak of 1-O-alkyl-2-O-alkylcarbomoylglycerol 0.80-1.20.

The content of 1-O-alkyl-2-O-alkylcarbomoylglycerol is calculated by the formula:

where a _i is the content of 1-O-alkyl-2-O-alkylcarbomoylglycerol in the substance;

S _i is the peak area of 1-O-alkyl-2-O-alkylcarbomoylglycerol in the chromatogram of the test solution;

S ₀ is the peak area of 1-O-alkyl-2-O-alkylcarbomoylglycerol in the chromatogram of a standard solution;

2- dilution coefficient;

and ₀ is a sample of 1-O-alkyl-2-O-alkylcarbomoylglycerol taken to prepare a standard solution in grams;

L is a sample of the substance taken for the preparation of the test solution in grams;

100 - coefficient for conversion to percent.

The result of the determination is the arithmetic average of at least three consecutive definitions. The content of 1-O-alkyl-2-O-alkylcarbomoylglycerol in 1 g should be from 98.5% to 101.5%.

From the chromatogram of the test solution, the peak area of each individual impurity — S _i , the sum of the areas of all peaks ΣS _i , the peak area of 1-O-alkyl-2-O-alkylcarbomoylglycerol — S is calculated. System peaks (retention coefficient less than 1) and peaks with an area of less than 0 , 02% are not taken into account.

The impurity content is calculated by the formula:

where b _i is the impurity content (in%) of the content of 1-O-alkyl-2-O-alkylcarbomoylglycerol;

S _i is the peak area of the impurity in the chromatogram of the test solution;

S ₀ is the peak area of 1-O-alkyl-2-O-alkylcarbomoylglycerol in the chromatogram of a standard solution;

2- dilution coefficient;

b ₀ - a portion of 1-O-alkyl-2-O-alkylcarbomoylglycerol taken to prepare a standard solution in grams;

L is a sample of the substance taken for the preparation of the test solution in grams;

100 - coefficient for conversion to percent.

Solution preparation

Mobile phase: 500 ml of chromatography water and 300 ml of acetonitrile (HLPC grade, Panreac, Cat.No. 221881.1612) and 200 ml of isopropyl alcohol (HLPC grade, Panreac, Cat.No. 221090.1612) are mixed into a 1000 ml volumetric flask, mixed and filtered through a membrane filter with a pore diameter of 0.45 μm. It is allowed to change the composition of the mobile phase to achieve the suitability of the chromatographic system.

A standard solution of 1-O-alkyl-2-O-alkylcarbomoylglycerol is prepared by dissolving an exact portion (12.5 mg) of PCO in the mobile phase in a 50 ml volumetric flask.

Test solution: an exact sample of the sample (25 mg) is transferred into a 100 ml flask, dissolved in the mobile phase and adjusted to the mark.

Justification of the mode

The use of a weaker base (pyridine pK _a 5.25) allows to increase the yield of the final product since this contributes to the selective attachment of the protective group at the 3 carbon atom of the 1-O-alkylglycerol molecule, which in turn leads to a more selective introduction of the alkylcarbomoyl group at the second carbon atom. In addition, the toxicity of pyridine (LD50 1580 mg / kg according to the National Institute for Occupational Safety and Health) is 3 times lower than that of triethylamine (LD50 460 mg / kg according to the National Institute for Occupational Safety and Health), which increases production safety .

Replacing the solvent for the chemical reaction with a more polar one (methylene chloride), due to improved solvation of the reaction intermediates proceeding according to the Sn ₂ mechanism, also contributes to an increase in the rate of the substitution process and an increase in the yield of the final product due to improved solvation of the reaction intermediates proceeding along the Sn ₂ -mechanism.

The experimental synthesis of 1-O-alkyl-2-O-alkylcarbomoylglycerols using these changes confirmed an increase in the yield of the target product to 98% and the purity of the target product from 98.9% (Table 1).

Annex 1

The method of obtaining 1-alkyl-2-alkylcarbamoylglycerols

Figure 1 - Scheme for the preparation of 1-O-alkyl-2-O-alkylcarbomoylglycerols

Table 1 - Change in the yield of the target product when using the claimed method

Claims (5)

The method of obtaining 1-alkyl-2-alkylcarbamoylglycerols of the General formula I

, where R ₁ is the hydrocarbon residue C16-C18; R ₂ is methyl, ethyl, which consists in the fact that the initial 1-alkylglycerols of the general formula II are reacted

with trimethylchlorosilane in the presence of a base in a solvent medium, characterized in that the starting 1-alkylglycerols are reacted with trimethylchlorosilane in the presence of pyridine, and methylene chloride is used as a solvent, the reaction is carried out in an atmosphere of air at 0 ° C, followed by addition of the corresponding alkyl isocyanate and subsequent treatment with a mixture of methanol-chloroform.

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