36 results about "Methyl tosylate" patented technology

The invention relates to a method for detecting genotoxic impurities in an AL58805 bulk drug or medicinal preparation by using high-performance liquid chromatography. The method is directed at methyl p-toluenesulfonate (MPTS) and ethyl p-toluenesulfonate (EPTS); a sample undergoes pre-treatment at first; and then high-performance liquid chromatography is employed for determination, wherein a C18 chromatographic column is employed; detection wavelength is 225 nm; an aqueous acetonitrile-phosphoric acid solution is used as a mobile phase; flow velocity is 0.8 to 1.2 mL / min; column temperature is 30 to 40 DEG C; a sample size is 20 [mu]L; and elution time is 18 min. Results show that the detection limit of MPTS is 0.3 ppm and the limit of quantitation of MPTS is 1 ppm; and the detection limit of EPTS is 0.5 ppm and the limit of quantitation of EPTS is 1.4 ppm. The method has the advantages of good specificity, simple operation, high sensitivity and accurate results and is applicable to determination of MPTS and EPTS in AL58805.

The invention discloses a high-yield high-purity DAST source powder synthetic process. The synthetic process comprises the following two steps: 1, reacting 4-methylpyridine with methyl p-toluenesulfonate in the presence of absolute ethyl alcohol serving as a solvent to obtain an absolute ethyl alcohol solution of 4-methyl-N-methylpyridine tosilate; and 2, reacting 4-methyl-N-methylpyridine tosilate with p-dimethylaminobenzaldehyde in the presence of absolute ethyl alcohol serving as a solvent and under the catalytic action of di-n-butylamine or piperidine, so as to obtain high-yield (85-95%) high-quality (90-95%) DAST source powder. According to the synthetic process, absolute ethyl alcohol is used as a reaction solvent, harm of poisonous and harmful solvents such as methylbenzene and methyl alcohol to the body of an operator can be avoided and the pollution of waste liquid to the environment can be avoided. The research success of the high-yield high-purity DAST source powder synthetic process is beneficial to culture of high-quality large-sized DAST crystal, thereby laying a good material and theoretical basis for research on the DAST crystal and related products.

A novel process for the synthesis of Lacosamide using D,L-serine as starting material is described, where the methylation reaction of hydroxyl is carried out using an inexpensive base such as NaOH and an inexpensive alkylating agent, non-toxic and non-carcinogenic, such as methyl p-toluenesulfonate; the R enantiomer is isolated from the racemic mixture of Lacosamide after selective hydrolysis of the acetamide, salification of the racemic mixture with a chiral acid (HX*) in an organic solvent, resolution of the diastereoisomeric mixture, preferably by precipitation of the R enantiomer, and subsequent acetylation of the optically pure intermediate.

The invention relates to a method for determining the content of methyl p-toluenesulfonate in a medicine, and concretely relates to a method for detecting the content of methyl p-toluenesulfonate in amedicine through headspace derivatization gas chromatography-mass spectrometry. The above derivatization method, using a mixed aqueous solution containing vitamin C and sodium iodide as a derivatization solution, has the advantages of wide suitable equilibrium temperature and equilibrium time range, high sensitivity, high precision, high accuracy, good durability, and easiness in operation, and can realize the accurate determination of the methyl p-toluenesulfonate in the medicine in order to ensure the safety of the medicine.

The invention discloses a synthetic method of 11 beta,17 alpha-dihydroxy-1,4-diene pregne-3,20-diketone-21-acetate. The invention employs 11 alpha-hydroxy-1,4-diene-16,17-epoxy progesterone (ii) as a starting material, which together with methyl p-toluenesulfonate is subjected to a Mitunobu reaction for inversion under the catalysis of diethyl azodiformate and triphenyl phosphine to obtain 11 beta-p-toluenesulfonyl-16,17 epoxy-1,4-diene progesterone (iii), namely a 11 beta-hydroxy protector; the (iii) is subjected to protective group removal in the presence of HBr, and 16,17-epoxy addition to obtain 11 beta, 17 alpha-dihydroxy-16 beta-bromo-1,4-allyl progesterone (iv); the (iv) is subjected to 3 steps to synthesize 11 beta,17 alpha-dihydroxy-1,4-diene pregne-3,20-diketone (v), which is added with iodine to obtain 11 beta,17 alpha-dihydroxy-1,4-diene pregne-3,20- diketone-21-iodine (vi); and the (vi) is subjected to replacement with potassium acetate to obtain the 11 beta,17 alpha-dihydroxy-1,4-diene pregne-3,20-diketone-21-acetate (i). The method provided by the invention can avoid complex strain breeding, has the advantages of simple operation, high yield, little environmental pollution, and has good industrial application prospect.

A new method for synthesizing methoxamine hydrochloride, the method steps: under the protection of nitrogen, add liquid methyl p-toluenesulfonate to a certain amount of potassium carbonate in acetonitrile solution, and control the temperature to 15°C±3°C , slowly drop into the mixture of acetonitrile containing an appropriate amount of hydroquinone. Stir for another 5 minutes, heat up to 83° C. and reflux vigorously for reaction. When reflux occurs, turn off the nitrogen gas, and the reaction will be complete within 22 hours. Then through Friedel-Crafts acylation reaction, oximation reaction, oxime group reduction reaction, ketoamine hydrogenation reaction, and finally the target product was synthesized by an economical and environmentally friendly route. The yields of the 5-step operations were: 94%, 72%, 80%, 79% and 88%, respectively. The invention has the advantages of mild reaction, simple conditions, stable and easy scale-up production, and improved yield compared with the traditional synthesis of methoxamine hydrochloride.

The invention relates to a novel synthesis process of pharmaceutical intermediate 3, 5-bi(2-cyanoindole-isopropyl)-toluene, belonging to the chemical synthesis technology field. The invention uses 5-methyl-1, 3-dimethyl phthalate as the material, synthesizes anastrozole intermediate 3, 5-bi(2-cyanoindole-isopropyl)-toluene by esterification, reduction, brominating, cyaniding and methylation reaction. The reduction method using borohydrides is performed in aether solvent, the method can completely avoid using high-toxicity solvent such as CCl4 or the like; in the methylation reaction, expensive iodomethane is replaced by p-toluenesulfonic acid methyl; the purity of product 3, 5-bi(2-cyanoindole-isopropyl)-toluene (2) is high.

The invention discloses a preparation method for a Clarithromycin intermediate. The method is characterized in that (2',4"-O-bistrimethylsilyl)-erythromycin A-9[O-(1-ethoxy-1-methylethyl)]oxime is used as a raw material, toluene, hexane and dimethyl sulfoxide are used as solvents, bromomethane, iodomethane and methyl p-toluenesulfonate are used as methylation reagents, potassium hydroxide is used as a catalyst, and methylation is carried out so as to prepare the Clarithromycin intermediate. According to the invention, through selection of a solvent system, cooperative control of the amounts of the reaction reagent and the catalyst and synergism of temperature and time, the preparation method for the Clarithromycin intermediate has the advantages of simple process, stable operation, a high conversion rate, low cost, a small amount of waste gas, waste water and industrial residue and suitability for industrial production.

The invention relates to a preparation method of a stable isotope labeled methotrexate internal standard reagent for monitoring the blood concentration of a clinical treatment drug, and belongs to the field of research and development of standard substances for monitoring the blood concentration of the clinical treatment drug. The preparation method comprises the following steps: by taking stable isotope labeled methyl p-toluenesulfonate as a raw material, carrying out addition, condensation and hydrolysis, and finally separating and purifying to obtain the stable isotope labeled methotrexate. The process route has the advantages that raw materials required for synthesis are simple and easy to obtain, reaction conditions are mild, a highly toxic methylation reagent is not used, and a final product is high in total yield and easy to separate and purify. The chemical purity of the final product stable isotope labeled methotrexate can reach 99% or above, and the isotope abundance can reach 99% or above. The stable isotope labeled methotrexate internal standard reagent prepared by the preparation method can meet the technical requirements of the stable isotope labeled internal standard reagent required by a liquid chromatography-tandem mass spectrometry method for monitoring the blood concentration of clinical treatment drugs.

The invention provides a polyurethane adhesive and a preparation method thereof. The polyurethane adhesive comprises diphenylmethane diisocyanate, styrene grafted polyether polyol, epoxide resin, methyl p-toluenesulfonate, polypropylene glycol, polyoxypropylene pentaerythritol ester, an amine catalyst, isophorone diamine, zeolite, castor oil, N-ethyl-N-zinc phenyl dithiocarbamate, resorcinol, triphenylphosphine, a silane coupling agent and an emulsifying agent. The preparation method comprises the following steps of: firstly mixing the diphenylmethane diisocyanate, the amine catalyst, the epoxide resin, the methyl p-toluenesulfonate, the polypropylene glycol, the polyoxypropylene pentaerythritol ester and the zeolite, and then adding the resorcinol and the triphenylphosphine; stirring, and then adding a mixture of the styrene grafted polyether polyol, the isophorone diamine, the castor oil, the N-ethyl-N-zinc phenyl dithiocarbamate, the silane coupling agent and the emulsifying agent to obtain the polyurethane adhesive. The polyurethane adhesive provided by the invention has the advantages of excellent yellowing resistance, ageing resistance, heat resistant property, hydrolysis resistant property and bonding strength.

The invention discloses a synthesis method of a novel anti-influenza drug baloxavir dipivoxil, which uses thiosalicylic acid compound 1 and 1-(halomethyl)-2,3-difluorobenzene compound 2 as starting materials Direct docking to obtain compound 3, and then use PPA ring closure to obtain 7,8-difluorodibenzo[b,e]thiapine-11(6H)-one compound 4, and then obtain the key compound 4 under the catalysis of chiral enzyme Chiral Thiazem Intermediate Compound 5. Then compound 5 is directly condensed with the key chiral fragment compound 6 by Mitsubobu reaction to obtain compound 7, and finally removes the alkyl protection and condenses with ((methoxycarbonyl) oxygen) 4-toluenesulfonic acid methyl ester to obtain the final product compound 9 bar loxavir dipivoxil. This synthetic route reduces the difficulty of enlarging the process operation of the route, reduces the generation of by-products, improves the product purity, and reduces the cost of the route. The specific route:

The invention discloses a high-yield high-purity DAST source powder synthetic process. The synthetic process comprises the following two steps: 1, reacting 4-methylpyridine with methyl p-toluenesulfonate in the presence of absolute ethyl alcohol serving as a solvent to obtain an absolute ethyl alcohol solution of 4-methyl-N-methylpyridine tosilate; and 2, reacting 4-methyl-N-methylpyridine tosilate with p-dimethylaminobenzaldehyde in the presence of absolute ethyl alcohol serving as a solvent and under the catalytic action of di-n-butylamine or piperidine, so as to obtain high-yield (85-95%) high-quality (90-95%) DAST source powder. According to the synthetic process, absolute ethyl alcohol is used as a reaction solvent, harm of poisonous and harmful solvents such as methylbenzene and methyl alcohol to the body of an operator can be avoided and the pollution of waste liquid to the environment can be avoided. The research success of the high-yield high-purity DAST source powder synthetic process is beneficial to culture of high-quality large-sized DAST crystal, thereby laying a good material and theoretical basis for research on the DAST crystal and related products.