CN117362170A - Preparation method of cable Ma Lutai intermediate - Google Patents
Preparation method of cable Ma Lutai intermediate Download PDFInfo
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- CN117362170A CN117362170A CN202311322489.XA CN202311322489A CN117362170A CN 117362170 A CN117362170 A CN 117362170A CN 202311322489 A CN202311322489 A CN 202311322489A CN 117362170 A CN117362170 A CN 117362170A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- 238000006467 substitution reaction Methods 0.000 claims abstract description 7
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims abstract description 5
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 3
- 230000002378 acidificating effect Effects 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical group CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000012280 lithium aluminium hydride Substances 0.000 claims 1
- -1 lithium aluminum hydride Chemical compound 0.000 claims 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical group [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims 1
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 claims 1
- 239000003513 alkali Substances 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- BNJOQKFENDDGSC-UHFFFAOYSA-N octadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCCCC(O)=O BNJOQKFENDDGSC-UHFFFAOYSA-N 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical group [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- QQHJDPROMQRDLA-UHFFFAOYSA-N hexadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCC(O)=O QQHJDPROMQRDLA-UHFFFAOYSA-N 0.000 description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- HQHCYKULIHKCEB-UHFFFAOYSA-N tetradecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCC(O)=O HQHCYKULIHKCEB-UHFFFAOYSA-N 0.000 description 2
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 1
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 235000009643 reducing diet Nutrition 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- GYBMSOFSBPZKCX-UHFFFAOYSA-N sodium;ethanol;ethanolate Chemical group [Na+].CCO.CC[O-] GYBMSOFSBPZKCX-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C51/38—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by decarboxylation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of a cable Ma Lutai intermediate, which comprises the following steps: s1, reacting a compound raw material of a formula I in the presence of a reducing agent to generate an intermediate of a formula II; s2, reacting the compound shown in the formula II with an organic solvent A under a substitution reagent and an alkaline condition to generate an intermediate shown in the formula III; s3, reacting the compound shown in the formula III with an iodized salt reagent in the presence of an organic solvent B to generate an intermediate shown in the formula IV; s4, reacting the compound shown in the formula IV with diethyl malonate in the presence of alkali and an organic solvent C to generate an intermediate shown in the formula V; s5, hydrolyzing and deacidifying the compound shown in the formula V under an acidic condition to obtain a cable Ma Lutai intermediate, wherein the synthesis method is stable and reliable, and the reaction condition is mild; the obtained product has high conversion rate and high purity; the reaction route is as follows:
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a cable Ma Lutai intermediate.
Background
Cord Ma Lutai cord Ma Lutai (Semaglutide) was developed by Norand Norde, which is originally used for treating diabetes and is a glucagon-like peptide 1 (GLP-1) receptor agonist capable of mimicking its effect, reducing hunger sensation, reducing diet, reducing caloric intake, and thus has remarkable effects in reducing weight. Wherein, the intermediate octadecanedioic acid of the cable Ma Lutai is used for synthesizing the cable Ma Lutai bulk drug.
First, a method of octadecanedioic acid is disclosed in chinese patent application publication No. CN112939762 a:
the hexadecanedioic acid is used as a starting material, the route is subjected to three steps of reactions to obtain an intermediate, the route has double condensation conditions in the condensation reaction process, the yield is low, the hexadecanedioic acid unit price is high, the cost is high, and the method is not suitable for industrialization.
Disclosure of Invention
The invention aims to provide a preparation method of a cable Ma Lutai intermediate, which has the advantages of simple operation, stable and reliable process, high purity of the obtained cable Ma Lutai intermediate, mild reaction conditions and suitability for industrial production.
The embodiment of the invention is realized by the following technical scheme:
a method of preparing a cord Ma Lutai intermediate comprising the steps of:
s1, reacting a compound raw material of a formula I in the presence of a reducing agent to generate an intermediate of a formula II;
s2, reacting the compound shown in the formula II with an organic solvent A under a substitution reagent and an alkaline condition to generate an intermediate shown in the formula III;
s3, reacting the compound shown in the formula III with an iodized salt reagent in the presence of an organic solvent B to generate an intermediate shown in the formula IV;
s4, reacting the compound shown in the formula IV with diethyl malonate in the presence of alkali and an organic solvent C to generate an intermediate shown in the formula V;
s5, hydrolyzing and deacidifying the compound shown in the formula V under an acidic condition to obtain a compound shown in the formula VI, namely a key intermediate of the cable Ma Lutai: octadecanedioic acid.
The reaction route is as follows:
preferably, in S2, the substitution reagent is TsCl or MsCl, most preferably MsCl.
Preferably, in S2, the molar ratio of the substitution reagent to formula II is from 2.2 to 3:1, most preferably 3:1.
Preferably, in S2, the alkaline reagent is Et3N, K 2 CO 3 Or t-BuOK, most preferably potassium carbonate.
Preferably, in S2, the organic solvent a is DMF, DCM or THF, most preferably THF.
Preferably, in S3, the molar ratio of the iodinated salt reagent to formula III is from 3 to 5:1, most preferably 4:1.
Preferably, in S3, the iodinated salt reagent is NaI or KI, most preferably KI.
Preferably, in S3, the organic solvent B is acetone, THF or ethyl acetate, most preferably acetone.
Preferably, in S4, the alkaline reagent is sodium ethoxide ethanol solution, K 2 CO 3 Or sodium methoxide, most preferably potassium carbonate.
Preferably, in S4, the organic solvent C is ethanol, DMF or methanol, most preferably DMF.
The technical scheme of the embodiment of the invention has at least the following advantages and beneficial effects:
1. the synthesis method of the cable Ma Lutai intermediate has the advantages of simple operation, stable and reliable process, good safety, good synthesis reaction selectivity, higher conversion rate and high purity of the obtained cable Ma Lutai intermediate, and can obviously inhibit the generation of byproducts.
2. The raw materials and the auxiliary materials are easy to obtain and low in price, heavy metal or noble metal substances are not adopted in the synthesis process, excessive pollution to the environment is avoided, and compared with the existing production route, the method has the advantages of low cost, mild reaction conditions and short period, and is suitable for industrial production.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1: synthesis of intermediate II
500ml of THF is added into a 1L three-mouth bottle, the temperature is reduced to 0+/-5 ℃, 11.72g of sodium borohydride is slowly added, the temperature is controlled to 0+/-5 ℃, 44g of boron trifluoride diethyl etherate solution is slowly added dropwise, the temperature is controlled to 0+/-5 ℃,20g of tetradecanedioic acid is slowly added, and after the dropwise addition is finished, the temperature is increased to 50 ℃ for reaction overnight; post-treatment: cooling to 0-5 ℃, slowly dripping 100ml of water for quenching reaction, slowly adding 6M HCl for regulating the pH value to 1-2, heating for reflux reaction for 4 hours, concentrating THF, cooling to 0+ -5 ℃, crystallizing for 4 hours, filtering to obtain 15.1g, and obtaining the yield of 85%.
Example 2: synthesis of intermediate III
Sequentially adding 20g of intermediate II,400mlTHF,36g potassium carbonate prepared in example 1 into a 1L three-necked flask, slowly dropwise adding 25g of MsCl, controlling the temperature to be 0+/-5 ℃, and after the dropwise adding is finished, moving to room temperature and reacting overnight; post-treatment: the mixture was filtered, the filter cake was rinsed with 50ml of THF, and the filtrate was collected and concentrated to dryness to give 30g of a white solid in 90% yield.
Example 3: synthesis of intermediate III
Sequentially adding 20g of intermediate II,400mlDCM,31g triethylamine prepared in example 1 into a 1L three-necked flask, slowly dropwise adding 30g of MsCl, controlling the temperature to be 0+/-5 ℃, and after dropwise adding, moving to room temperature and reacting overnight; post-treatment: the mixture was filtered and the filter cake was rinsed with 50ml of DCM, and the filtrate was collected and concentrated to dryness to give 28.3g of a white solid in 85% yield.
Example 4: synthesis of intermediate III
Sequentially adding 20g of intermediate II,400mlTHF,36g potassium carbonate prepared in example 1 into a 1L three-necked flask, slowly dropwise adding 30g of MsCl, controlling the temperature to be 0+/-5 ℃, and after the dropwise adding is finished, moving to room temperature and reacting overnight; post-treatment: the mixture was filtered, the filter cake was rinsed with 50ml of THF, and the filtrate was collected and concentrated to dryness to give 31.7g of a white solid in 95% yield.
Example 5: synthesis of intermediate IV
20g of the intermediate III,400ml THF,38.78g sodium iodide prepared in example 2 is sequentially added into a 1L three-necked flask, and the mixture is heated to reflux and reacted overnight; post-treatment: filtration and concentration of the filtrate to an oil gave 18.63g in 80% yield.
Example 6: synthesis of intermediate IV
20g of intermediate III prepared in example 3, 400ml of acetone and 34.36g of potassium iodide are sequentially added into a 1L three-necked flask, and the mixture is heated to reflux and reacted overnight; post-treatment: filtration and concentration of the filtrate to an oil gave 21.66g in 93% yield.
Example 7: synthesis of intermediate V
240mL of DMF,20g of intermediate IV prepared in example 5, 15.63g of diethyl malonate and 18.39g of potassium carbonate are sequentially added into a 500mL three-necked flask, and the mixture is stirred and heated to 60+/-5 ℃ for reaction overnight; post-treatment: cooling to room temperature, adding 80ml of purified water and 60ml of ethyl acetate for extraction, extracting the water phase with 60ml of ethyl acetate twice, combining the organic phases, drying the organic phases by anhydrous magnesium sulfate, filtering, concentrating the filtrate until the oily matter is obtained, and obtaining 22.16g, and the yield is 97%.
Example 8: synthesis of intermediate V
240mL of methanol, 20g of intermediate IV prepared in example 6, 15.63g of diethyl malonate and 7.2g of sodium methoxide are sequentially added into a 500mL three-necked flask, and the mixture is stirred and heated to 60+/-5 ℃ for reaction overnight; post-treatment: cooling to room temperature, adding 80ml of purified water and 60ml of ethyl acetate for extraction, extracting the water phase with 60ml of ethyl acetate twice, combining the organic phases, drying the organic phases by anhydrous magnesium sulfate, filtering, concentrating the filtrate until the oily matter is obtained, and obtaining 20.1g, and the yield is 88%.
Example 9: synthesis of intermediate VI
20g of intermediate V prepared in example 8, 80mL of acetic acid and 80mL of concentrated hydrochloric acid are sequentially added into a 500mL three-necked flask, stirred and heated to reflux, and reacted overnight; post-treatment: the reaction solution was cooled to room temperature, and solids were precipitated, filtered, and the cake was collected to give 10.75g, with a yield of 88% and a purity of 99.5%.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for preparing a cable Ma Lutai intermediate, which is characterized by comprising the following steps: the method comprises the following steps:
s1, taking a compound in a formula I as a raw material, and reacting under the condition of a reducing agent to generate an intermediate in a formula II, wherein the reaction equation is as follows:
s2, reacting the intermediate of the formula II under the conditions of an organic solvent A, a substitution reagent and alkalinity to generate an intermediate of the formula III, wherein the reaction equation is as follows:
wherein R is Ts, ms;
s3, reacting the intermediate of the formula III with an iodized salt reagent under the condition of an organic solvent B to generate an intermediate of the formula IV, wherein the reaction equation is as follows:
wherein R is Ts, ms;
s4, reacting the intermediate of the formula IV with diethyl malonate under the conditions of an organic solvent C and alkalinity to generate an intermediate of the formula V, wherein the reaction equation is as follows:
s5, deacidifying the compound shown in the formula V under an acidic condition, and reacting to generate the compound shown in the formula VI, wherein the reaction equation is as follows:
。
2. the method of claim 1, wherein in S1, the reducing agent is one or more of sodium borohydride, lithium aluminum hydride, or sodium borohydride triacetate.
3. A process for the preparation of a cable Ma Lutai intermediate according to claim 1, wherein in S1 the molar ratio of reducing agent to compound of formula I is: 1:2.2-2.5.
4. A process for the preparation of a cable Ma Lutai intermediate according to claim 1, wherein in S2 the substitution reagent is TsCl or MsCl; the alkaline reagent is Et3N, K 2 CO 3 Or t-BuOK; the organic solvent A is DMF, DCM or THF.
5. A process for the preparation of a cable Ma Lutai intermediate according to claim 1, wherein in S2 the molar ratio of substitution reagent to formula II is from 2.2 to 3:1.
6. the process for preparing a cord Ma Lutai intermediate as claimed in claim 1, wherein in S3 the molar ratio of the iodinated salt reagent to formula III is 3-5:1.
7. a process for the preparation of a cord Ma Lutai intermediate as claimed in claim 1, wherein in S3 the iodinated salt reagent is NaI or KI.
8. The process for preparing a cable Ma Lutai intermediate as claimed in claim 1, wherein in S3, the organic solvent B is acetone, THF or ethyl acetate.
9. The process for preparing a cable Ma Lutai intermediate as claimed in claim 1, wherein in S4, the alkaline agent is sodium ethoxide solution, K 2 CO 3 Or sodium methoxide.
10. The process for preparing a cable Ma Lutai intermediate as claimed in claim 1, wherein in S4, the organic solvent C is ethanol, DMF or methanol.
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