CN108409615B - Method for synthesizing enantiopure tert-butyl sulfenamide - Google Patents
Method for synthesizing enantiopure tert-butyl sulfenamide Download PDFInfo
- Publication number
- CN108409615B CN108409615B CN201810450652.3A CN201810450652A CN108409615B CN 108409615 B CN108409615 B CN 108409615B CN 201810450652 A CN201810450652 A CN 201810450652A CN 108409615 B CN108409615 B CN 108409615B
- Authority
- CN
- China
- Prior art keywords
- tert
- butyl
- synthesis
- enantiomerically pure
- butylsulfinamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C313/02—Sulfinic acids; Derivatives thereof
- C07C313/06—Sulfinamides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C313/02—Sulfinic acids; Derivatives thereof
- C07C313/04—Sulfinic acids; Esters thereof
Abstract
The invention discloses a method for synthesizing enantiopure tertiary butyl sulfinamide, which comprises the steps of selectively oxidizing tertiary butyl disulfide and hydrogen peroxide, then obtaining tertiary butyl sulfinyl chloride or tertiary butyl sulfinyl bromide with an acylation reagent, then obtaining tertiary butyl sulfinyl hydrazine with hydrazine hydrate, then carrying out resolution and dissociation with a DTTA resolving agent, and obtaining enantiopure tertiary butyl sulfinamide after zinc/acetic acid cracking. The method has the advantages of simple and stable process operation, high yield, environmental friendliness, cheap and easily-obtained raw materials compared with the conventional process, reduction of the production cost of the conventional enantiopure tert-butyl sulfenamide, and contribution to industrial mass production.
Description
Technical Field
The invention belongs to the technical field of drug synthesis, and particularly relates to a method for synthesizing enantiopure tert-butyl sulfenamide.
Background
Tert-butyl sulfenamide, known as 2-methylpropane-2-sulfenamide, has the molecular formula: (CH3)3CSONH 2. The chiral tertiary butyl sulfinamide comprises R type and S type chiral configurations, is an important chemical used as a chiral auxiliary group, and has important significance and function in academic chiral synthesis, chiral drug synthesis and industrial industry.
Nowadays, most drugs or drug intermediates have amine groups, which is an important chiral prosthetic group chemical in asymmetric synthesis. In the general view of recent academic reports and the new drugs on the market, more and more drugs are available which use enantiomerically pure tert-butylsulfinamides. For example: the academic reports show that the method has application in synthesis of paclitaxel and synthesis of the antiallergic drug cetirizine hydrochloride. Chiral tert-butyl sulfinamide is also increasingly used as an auxiliary agent for constructing chiral amine in clinical and marketed new drugs.
The enantiopure tertiary butyl sulfinamide documents are reported and mainly divided into two types, wherein the synthetic route of one type is as follows:
the preparation method comprises the steps of using tert-butyl mercaptan as a raw material, oxidizing the tert-butyl mercaptan by using a catalyst and hydrogen peroxide, then carrying out asymmetric oxidation by using the hydrogen peroxide, a vanadium catalyst and a chiral ligand to obtain chiral tert-butyl thiosulfinate, and then obtaining optically pure tert-butyl sulfinamide under the cryogenic condition of liquid ammonia, metal lithium and ferric nitrate.
The reaction equation is as follows:
in the above method, the time of the asymmetric chiral oxidation process of the tert-butyl disulfide is too long (about 4 days), and the above method has the main problems that the usage amount of liquid ammonia is too large, the ammonia discharge process is not suitable for recycling, the environment is polluted, and the tert-butyl mercaptan which generates foul odor after the reaction is finished causes serious environmental problems.
Another synthetic route to enantiomerically pure tert-butylsulfinamide is reported in the literature as follows:
the method comprises the steps of taking cis-form chiral indene amine alcohol as a raw material, protecting amino, reacting with thionyl chloride, carrying out nucleophilic attack on the cis-form chiral indene amine alcohol and a tert-butyl Grignard reagent, and finally obtaining enantiomorphous pure tert-butyl sulfinamide under the cryogenic condition of liquid ammonia, metal lithium and ferric nitrate. The reaction equation is as follows:
in the method, the production of the foul odor tert-butyl mercaptan is not involved, but the cost is high, the whole steps are long, and the mass production is not facilitated.
Disclosure of Invention
Aiming at the defects in the prior art and overcoming the defects of the compound synthesis process, the invention provides the synthesis method which is simple, convenient and stable to operate, environment-friendly, low in production cost, high in atom and suitable for industrial scale production of enantiopure tert-butyl sulfinamide.
The invention provides a method for synthesizing enantiopure tert-butyl sulfinamide. The representative reaction equation is as follows:
the technical scheme is realized by the following steps:
the first step is the synthesis of tert-butylthiosulfinate.
Adding p-tert-butyl disulfide and VO (acac)2 into ethanol or a solvent of p-tert-butyl disulfide and acetic acid, and dropwise adding hydrogen peroxide at 25 ℃ to react completely to obtain tert-butyl thiosulfinate; wherein the reaction temperature is selected from 25 ℃ to 35 ℃.
Second step synthesis of tert-butylsulfinyl chloride/bromine.
Adding an acylating reagent into tert-butyl thiosulfinate at 0 ℃ to react to obtain tert-butyl sulfinyl chloride or tert-butyl sulfinyl bromide, wherein the reaction temperature is selected from 0 ℃ to 10 ℃.
And step three, synthesizing tert-butylsulfinyl hydrazide.
Adding tert-butyl sulfinyl chloride or tert-butyl sulfinyl bromide into hydrazine hydrate at 0 ℃ to react to obtain tert-butyl sulfinyl hydrazine, wherein the reaction temperature is selected from 0 ℃ to 30 ℃.
And fourthly, carrying out salifying resolution and dissociation on the tert-butylsulfinyl hydrazide.
Adding tert-butylsulfinyl hydrazide into an organic solvent, dropwise adding the tartaric acid resolving agent solution at 30 ℃, refluxing for 3 hours after dropwise adding, and slowly cooling to obtain chiral tert-butylsulfinyl hydrazide complex salt. Wherein the reaction temperature is selected from 0 ℃ to 68 ℃. Then the enantiomorphous pure tert-butyl sulfuryl hydrazine is obtained by dissociation.
The fifth step is the synthesis of enantiomerically pure tert-butylsulfinamide.
Adding chiral optically pure tert-butylsulfinyl hydrazide into acetic acid and zinc powder, and reacting at 40-45 ℃ to obtain the enantiopure tert-butylsulfinamide, wherein the reaction temperature is selected from 40-45 ℃.
Further, in the above technical scheme, the acylating agent in the second step reaction is selected from NBS, NCS, bromine or chlorine, and the molar ratio of tert-butyl thiosulfinate to acylating agent is: 1:0.98-1.02.
Further, in the above technical solution, the derivative series resolving agent in the fourth step is selected from tartaric acid, DBTA and DTTA. When splitting, 1 equivalent or 0.5 equivalent of splitting agent is adopted to split respectively, and the EE of the split salified product is greater than 90 percent as the standard.
Wherein DBTA is Dibenzoyl-L-tartanic acid (DBTA) for short; DTTA is Di-p-toluoyl-tartaric acid (Di-p-toluoyl-tartaric acid) for short; both resolving agents include their hydrate forms.
Further, in the technical scheme, the product is pulped at low temperature by adopting a mixed solvent of n-heptane and toluene to obtain a pure product with the purity of 99 percent and the EE of more than 99 percent, and the mass ratio of the mixed solvent of n-heptane and toluene is 6: 1-1.5.
The invention has the beneficial effects that:
compared with the prior synthesis method, the invention has the following beneficial effects:
1) the invention has simple synthetic route and easily obtained raw materials, particularly greatly reduces the reaction time of the tert-butyl thiosulfinate, greatly facilitates the industrial amplification production and saves the cost.
2) The tert-butylsulfinyl hydrazide obtained by the method is suitable for purification of products and mild in reaction conditions.
3) The method avoids cryogenic reaction through the improvement of the resolution, and has simple operation and high atom utilization rate. The solvent and the resolving agent can be recycled and reused, the yield of the product is greatly improved, and the method is more suitable for industrial amplification.
Detailed Description
The invention is further illustrated by the following specific examples.
These examples are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. After reading the description of the invention, one skilled in the art can make various changes and modifications to the invention, and such equivalent changes and modifications also fall into the scope of the invention defined by the claims.
The experimental methods of the present invention, in which specific conditions are not specified in the following examples, are generally carried out under conventional conditions.
The starting materials or reagents used in the following examples of the present invention are commercially available unless otherwise specified.
The average room temperature described in the following examples of the present invention is 20-35 ℃. Unless otherwise indicated, the reagents are not specifically indicated and are all used without purification. All solvents were purchased from commercial suppliers and used without treatment. The reaction was analyzed by TLC, GC, HPLC and the end of the reaction was judged by the consumption of starting material.
Example 1
The first step is as follows: synthesis of tert-butyl thiosulfinate.
(1) Adding 180g of tert-butyl disulfide, 1.8g of VO (acac)2 and 400mL of ethanol into a reaction bottle in sequence, dropwise adding 138.5g of 27% hydrogen peroxide at 25 ℃, reacting for 7 hours at 30-35 ℃, sampling TLC or HPLC (high performance liquid chromatography) detection, reducing the pressure of the raw material to less than 1.5%, concentrating, washing with saturated sodium chloride once, adding 400g of dichloromethane to dilute sodium sulfate, and drying for later use. The external standard yield is 88%.
(2) Adding 180g of tert-butyl disulfide and 420mL of acetic acid into a reaction bottle in sequence, dropwise adding 150.1g of 27% hydrogen peroxide at 25 ℃, reacting for 3 hours at 30-35 ℃, sampling TLC or HPLC (high performance liquid chromatography) for detection, pouring the raw materials of which the content is less than 1% into 500g of water, extracting with dichloromethane, washing with saturated sodium chloride once, and drying with sodium sulfate for later use. The external standard yield is 93 percent.
The second step is that: synthesis of tert-butylsulfinyl bromide/chloride.
(1) A dichloromethane solution containing 108.6g of tert-butyl thiosulfinate (calculated by external standard yield) is added into a reaction bottle, 89.6g of bromine is added dropwise at 0 ℃, the reaction is carried out for 1 hour at 5-10 ℃, sampling GC or HPLC detection after derivatization does not leave raw materials, reduced pressure distillation is carried out, fractions are collected at 64-71 ℃, 96.3g of tert-butyl sulfinyl bromide is obtained, and the yield is 95%. The tert-butyl sulfinyl bromide is suitable for deterioration and needs to be stored under low-temperature inert gas.
(2) A dichloromethane solution containing 108.6g of tert-butyl thiosulfinate (calculated by external standard yield) is added into a reaction bottle, 39.4g of chlorine gas is introduced at 0 ℃, the reaction is carried out for 1 hour at 5-10 ℃, no raw material is left by sampling GC or HPLC detection after derivatization, reduced pressure distillation is carried out, and fractions are collected at 58-67 ℃ to obtain 68.2g of tert-butyl sulfinyl chloride, wherein the yield is 87%. Storing under inert gas at low temperature for use.
(3) A dichloromethane solution containing 108.6g of tert-butyl thiosulfinate (calculated by external standard yield) is added into a reaction bottle, 101.6g of NBS is added in batches at 5 ℃, the reaction is carried out for 1 hour at 5-10 ℃, the residual of the raw materials is less than 0.5 percent by sampling GC or HPLC detection after derivatization, the obtained tert-butyl sulfinyl bromide is directly used for the next step without treatment, and the external standard yield is 91 percent. Storing under inert gas at low temperature for use.
(4) A dichloromethane solution containing 108.6g of tert-butyl thiosulfinate (calculated by external standard yield) is added into a reaction bottle, 76.3g of NCS is added in batches at 5 ℃, the reaction is carried out for 1 hour at 5-10 ℃, the residual of the raw materials is less than 0.5 percent by sampling GC or HPLC detection after derivatization, the obtained tert-butyl sulfinyl chloride is directly used for the next step without treatment, and the external standard yield is 93 percent. Storing under inert gas at low temperature for use.
The third step: and (3) synthesizing tert-butylsulfinyl hydrazide.
(1) And (2) adding 50g of 80% hydrazine hydrate and 85g of water into a reaction bottle in sequence, dropwise adding 35g of tert-butylsulfonyl chloride solution diluted by 45g of toluene in the second step (2), controlling the temperature to be between-5 and 15 ℃, dropwise adding, reacting for 2 hours at 20 to 25 ℃ after dropwise adding, sampling, detecting by TLC (thin layer chromatography) until no raw material is left, standing, partitioning upper-layer toluene (containing impurities), extracting lower-layer aqueous phase dichloromethane, and concentrating to obtain 37g of tert-butylsulfinylhydrazide with the yield of 89%. The tert-butylsulfinyl hydrazide is easy to deliquesce and needs to be stored at low temperature.
(2) And (2) sequentially adding 50g of 80% hydrazine hydrate and 85g of water into a reaction bottle, dropwise adding a dichloromethane solution containing 46.0g of tert-butylsulfonyl bromide in the second step (3), controlling the temperature to be between-5 and 15 ℃, dropwise adding, reacting for 2 hours at 20 to 25 ℃ after dropwise adding, sampling, detecting by TLC (thin layer chromatography) until no raw material is left, concentrating at 25 to 35 ℃ under reduced pressure until no liquid is distilled, adding toluene to extract impurities, partitioning upper toluene (containing impurities), extracting lower aqueous phase by dichloromethane, and concentrating to obtain 41g of tert-butylsulfinyl hydrazide with the yield of 91%. The tert-butylsulfinyl hydrazide is easy to deliquesce and needs to be stored at low temperature.
The fourth step: resolving tert-butylsulfinyl hydrazide to form salt and dissociating.
(1) Adding 150g of 2-methyltetrahydrofuran and 27.5g of tert-butylsulfuryl hydrazide into a reaction bottle, dropwise adding 39g (0.5eq) of a solution of L-DTTA dissolved in 150g of 2-methyltetrahydrofuran, controlling the dropwise adding temperature to be 30-45 ℃, keeping the temperature at 78 ℃ for 3 hours after the dropwise adding is finished, gradually cooling to 5-10 ℃, filtering, leaching 2-methyltetrahydrofuran, thermally pulping the product with 150g of 2-methyltetrahydrofuran, cooling, filtering and drying to obtain 42g of a resolved product, wherein the yield is 41 percent, and EE is 93 percent. The resulting mixture was hydrolyzed with 4N aqueous hydrochloric acid to adjust pH to 3-4, followed by extraction with toluene and recovery of L-DTTA, and the aqueous phase was adjusted with aqueous NaOH to adjust pH to 9-10, followed by extraction with dichloromethane to give 10.1g of(s) -tert-butylsulfinylhydrazide in a cleavage yield of 86%, EE 94%, and HPLC 98.7%.
(2) Adding 140g of ethyl acetate and 27.5g of tert-butylsulfinyl hydrazide into a reaction bottle, dropwise adding 36.2g (0.5eq) of D-DBTA solution in 140g of ethyl acetate, controlling the dropwise adding temperature to be 30-45 ℃, keeping the temperature at 74 ℃ for 3 hours after the dropwise adding is finished, slowly reducing the temperature to 15-20 ℃ in a gradient manner, filtering, leaching by using ethyl acetate, recrystallizing wet products by using 150g of ethyl acetate to obtain 36g of resolved products, wherein EE is 97%, and the yield is 37%. Hydrolyzing with 4N hydrochloric acid water solution, adjusting pH to 3-4, extracting with toluene to obtain D-DBTA, recycling, adjusting pH of water phase to 9-10 with NaOH water solution, extracting with dichloromethane to obtain 9.0g R-tert-butylsulfinylhydrazide, dissociation yield 85%, EE 99%, HPLC 99.1%.
(3) 160g of ethanol, 3g of water and 27.5g of tert-butylsulfinyl hydrazide are added into a reaction bottle, 30.2g (1eq) of a solution of L-Tartarric acid dissolved in 140g of ethanol is dropwise added, the dropwise adding temperature is controlled to be 30-45 ℃, after the dropwise adding is finished, the temperature is kept at 76 ℃ for 3 hours, the temperature is gradually reduced to 0-10 ℃, the filtration is carried out, then 30g of cold ethanol is used for leaching, the product is dried, 24.8g of resolved product is obtained, EE is 89%, and the yield is 43%. Hydrolysis was performed with an aqueous NaOH solution, and methylene chloride was extracted to obtain 10.7g of(s) -tert-butylsulfinylhydrazide, which had HPLC 98.3%, EE 91%, and dissociation yield 89%.
(4) Adding the salifying mother liquor filtered in the fourth step (3) into a reaction bottle, concentrating to dryness, adding a small amount of ethyl acetate, pulping, filtering to obtain 32.3g of solid, hydrolyzing by using an NaOH aqueous solution, extracting by using dichloromethane to obtain 14.6g of tert-butylsulfinyl hydrazide, adding 90g of ethanol and 1g of water, dropwise adding a solution of 16.1g (1eq) of D-Tartarric acid in 70g of ethanol, controlling the dropwise adding temperature to be 30-45 ℃, keeping the temperature at 76 ℃ for 3 hours after the dropwise adding is finished, slowly cooling to 0-10 ℃ in a gradient manner, filtering, leaching by using 10g of cold ethanol, drying the product to obtain 23.9g of resolved product, wherein the EE is 97%, and the yield is 78%. Hydrolysis was performed with an aqueous NaOH solution, and methylene chloride was extracted to obtain 10.1g of (r) -tert-butylsulfinylhydrazide, which had HPLC 99.3%, EE 98%, and dissociation yield 88%.
The fifth step: synthesis of enantiomerically pure tert-butylsulfinamide.
(1) Adding 70g of acetic acid, 42g R-tert-butylsulfinyl hydrazide, 60.5g of zinc powder and 150mL of dichloromethane into a reaction bottle, slowly heating to 35-42 ℃, reacting for 16 hours, sampling and detecting by HPLC, wherein the raw material is less than 2%, filtering, pouring the filtrate into 70mL of water, adding 75g of dichloromethane each time for extraction, extracting for 5 times, enriching an organic phase, adding 48% of NaOH to adjust the pH to 7-8, adding NaCl, adjusting to a saturated state, layering, washing the organic phase for 1 time by 15g of saturated sodium chloride aqueous solution, drying by magnesium sulfate, filtering, concentrating the filtrate under reduced pressure at 25-30 ℃ until the filtrate is not distilled, replacing n-heptane, adding 28g of mixed solvent of n-heptane and toluene (n-heptane: toluene: 6: 1), pulping at low temperature, filtering to obtain a white crystalline solid with the HPLC purity of 99.3%, EE of 99.7% (R) -tert-butylsulfinamide of 30.9g, the yield is 83 percent, and the HNMR structure is in accordance with the formula.
(2) Adding 70g of acetic acid, 42g S-tert-butylsulfinyl hydrazide, 60.5g of zinc powder and 150mL of dichloromethane into a reaction bottle, slowly heating to 35-42 ℃, reacting for 16 hours, sampling and detecting by HPLC, wherein the raw material is less than 2%, filtering, pouring the filtrate into water containing 70mL, adding 75g of dichloromethane each time for extraction, extracting for 5 times, enriching the organic phase, adding 48% of NaOH to adjust the pH to 7-8, adding NaCl, adjusting to a saturated state, layering, washing the organic phase for 1 time by 15g of saturated sodium chloride aqueous solution, drying by magnesium sulfate, filtering, concentrating the filtrate at 25-30 ℃ under reduced pressure to obtain a non-distilled liquid, replacing by n-heptane, adding 28g of n-heptane and toluene mixed solvent (n-heptane: toluene 6: 1), pulping at low temperature, filtering to obtain the product with the purity of HPLC of 99.5%, and EE of 99.1% (S) -tert-butylsulfinamide 28.3g, white crystalline solid, yield 76%, HNMR structure.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be able to cover the technical solutions and the inventive concepts of the present invention within the technical scope of the present invention.
Claims (6)
1. A method for synthesizing enantiomerically pure tert-butyl sulfenamide, comprising: 1) tert-butyl disulfide and hydrogen peroxide are selectively oxidized to obtain tert-butyl thiosulfinate; 2) adding an acylation reagent to obtain tert-butylsulfuryl halide; 3) then reacting with hydrazine hydrate to obtain tert-butylsulfinyl hydrazine; 4) carrying out salt-forming resolution dissociation by using a DTTA resolving agent; 5) the enantiopure tert-butyl sulfinamide is obtained by zinc/acetic acid reduction.
2. A process for the synthesis of enantiomerically pure tert-butylsulfinamide according to claim 1, characterized in that: the acylating agent is selected from NBS, NCS, bromine or chlorine.
3. A process for the synthesis of enantiomerically pure tert-butylsulfinamide according to claim 1, characterized in that: the first step reaction adopts VO (acac)2Oxidation is carried out or in an acetic acid solution.
4. A process for the synthesis of enantiomerically pure tert-butylsulfinamide according to claim 1, characterized in that: the molar ratio of tert-butyl thiosulfinate to acylating agent is 1: 0.98-1.02.
5. A process for the synthesis of enantiomerically pure tert-butylsulfinamide according to claim 1, characterized in that: when in resolution, 1 equivalent or 0.5 equivalent of resolving agent is adopted for resolution.
6. A process for the synthesis of enantiomerically pure tert-butylsulfinamide according to claim 1, characterized in that: the product is pulped at low temperature by adopting a mixed solvent of n-heptane and toluene to further improve the purity and EE, and the mass ratio of the mixed solvent of n-heptane and toluene is 6: 1-1.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810450652.3A CN108409615B (en) | 2018-05-11 | 2018-05-11 | Method for synthesizing enantiopure tert-butyl sulfenamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810450652.3A CN108409615B (en) | 2018-05-11 | 2018-05-11 | Method for synthesizing enantiopure tert-butyl sulfenamide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108409615A CN108409615A (en) | 2018-08-17 |
| CN108409615B true CN108409615B (en) | 2020-09-11 |
Family
ID=63138897
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810450652.3A Active CN108409615B (en) | 2018-05-11 | 2018-05-11 | Method for synthesizing enantiopure tert-butyl sulfenamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108409615B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112279791A (en) * | 2020-12-30 | 2021-01-29 | 和鼎（南京）医药技术有限公司 | Method for preparing chiral tert-butyl sulfinamide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1007503B (en) * | 1953-07-14 | 1957-05-02 | Bayer Ag | Process for the polymerization of monomeric vinyl compounds, preferably in the presence of polymer powders, in block, solution or in bead form |
| CN101525308A (en) * | 2009-04-20 | 2009-09-09 | 上海立科化学科技有限公司 | Method for synthesizing chiral sulfenamide |
-
2018
- 2018-05-11 CN CN201810450652.3A patent/CN108409615B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1007503B (en) * | 1953-07-14 | 1957-05-02 | Bayer Ag | Process for the polymerization of monomeric vinyl compounds, preferably in the presence of polymer powders, in block, solution or in bead form |
| CN101525308A (en) * | 2009-04-20 | 2009-09-09 | 上海立科化学科技有限公司 | Method for synthesizing chiral sulfenamide |
Non-Patent Citations (6)
| Title |
|---|
| "DMAP-Catalysed Sulfinylation of Diacetone-D-Glucose: Improved Method for the Synthesis of Enantiopure tert -Butyl Sulfoxides and tert-Butanesulfinamides";Ahmed Chelouan等;《Eur. J. Org. Chem.》;20140916;第6935-6944页 * |
| "Subtilisin-Catalyzed Resolution of N-Acyl Arylsulfinamides";Christopher K. Savile等;《J. AM. CHEM. SOC.》;20051231;第127卷;第2104-2113页 * |
| "基于各种拆分方法的四氢异喹啉生物碱、手性亚磺酰胺和顺式哌虫啶的合成研究";朱瑞恒;《中国博士学位论文全文数据库 工程科技I辑》;20140615(第6期);全文 * |
| "手性叔丁基亚磺酰胺的制备及其双亚胺的金属有机试剂不对称加成反应的研究";孙晓霞;《中国科学院成都有机化学研究所博士学位论文》;20051018;全文 * |
| 叔丁基磺酰胺的合成;桂厚瑛等;《石油化工》;20100615(第06期);第661-663页 * |
| 手性叔丁基亚磺酰胺的制备方法及其在药物合成中的应用;刘强等;《药学进展》;20131025(第10期);第493-500页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108409615A (en) | 2018-08-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114805314B (en) | Synthesis method of Entecavir | |
| CN109516998B (en) | Synthesis method of Barosavir intermediate | |
| CN113999142B (en) | Preparation method of chiral N-Boc-trans-1, 2-cyclohexanediamine | |
| CN108467353B (en) | Preparation method of enantiopure tert-butyl sulfinamide | |
| CN108558715B (en) | Method for preparing enantiopure tert-butyl sulfenamide | |
| CN108409615B (en) | Method for synthesizing enantiopure tert-butyl sulfenamide | |
| CN111072499B (en) | Synthesis process of ambroxol hydrochloride | |
| CN113416150A (en) | Novel synthesis method of lobaplatin intermediate | |
| CN108440349B (en) | Preparation method of chiral optical pure p-toluenesulfinamide | |
| CN103923040B (en) | A kind of method preparing furfural oxime acid | |
| CN114315609B (en) | Technological method for preparing cis-2-aminocyclohexanol | |
| CN106883192B (en) | The synthetic method of the benzoic acid derivative of nitrogenous class heterocyclic antineoplastic pharmaceutical actives oxazolyl modification | |
| CN115233243A (en) | Preparation method of 2,4, 5-trisubstituted oxazole derivative under electrocatalysis | |
| CN108558714B (en) | Preparation method of chiral optical pure p-toluenesulfinamide | |
| CN110183368A (en) | The synthetic method of (3R, 4S) -1- fluorenylmethyloxycarbonyl -4- N-ethyl pyrrole N -3- carboxylic acid suitable for industrialization | |
| CN111533656A (en) | Synthesis method of tert-butyl 4-methoxy-3-oxobutyrate | |
| CN111039838B (en) | Preparation method of 3-acetylmercapto-2-methylpropanoic acid | |
| CN111662233B (en) | Method for synthesizing 4-chloro-1H-imidazole-2-carboxylic acid ethyl ester by one-step method | |
| CN114516830B (en) | Preparation method and application of risedronic acid | |
| CN108484455B (en) | Method for synthesizing chiral optical pure p-toluenesulfinamide | |
| CN113072471B (en) | Lifeiste intermediate and preparation method thereof | |
| CN110590641B (en) | Green preparation method of 3-hydroxyisoindole-1-ketone series compounds | |
| KR100297802B1 (en) | Method for preparing 2- (3-trifluoromethyl) anilinonicotinic acid 2- (N-morpholine) ethyl. | |
| CN105001108B (en) | The preparation method of the dimethyl glutamate derivatives of optical voidness 3,4 | |
| CN114890930A (en) | Synthesis method of pyrroltinib intermediate (R, E) -3- (1-methylpyrrolidine-2-yl) acrylic acid hydrochloride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Sun Fuyuan Inventor after: Gao Feng Inventor after: Zeng Sailan Inventor before: Gao Feng Inventor before: Zeng Sailan |
|
| CB03 | Change of inventor or designer information | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20200814 Address after: 116200 Songhai street, songmudao chemical industry park, Jinpu New District, Dalian City, Liaoning Province Applicant after: Dalian Shuangbo Pharmaceutical Chemical Co.,Ltd. Address before: 201512 Shanghai City, Jinshan District Jinshanwei town Qiushi Road No. 688 Building 1, unit 2, room 404 Applicant before: SHANGHAI TBBMED Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |