AU2018100827A4 - Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method - Google Patents
Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method Download PDFInfo
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- AU2018100827A4 AU2018100827A4 AU2018100827A AU2018100827A AU2018100827A4 AU 2018100827 A4 AU2018100827 A4 AU 2018100827A4 AU 2018100827 A AU2018100827 A AU 2018100827A AU 2018100827 A AU2018100827 A AU 2018100827A AU 2018100827 A4 AU2018100827 A4 AU 2018100827A4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
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Abstract
Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method Abstract The present invention discloses drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, comprises the following steps:2-bromo-3 -methoxy-4-benzyloxy-4'-methyl diphenyl ether, sodium bromide solution were added to the reaction vessel, controlled the stirring rate, raised 10 the solution temperature, reacted; then added the benzyl phthalate solution, added palladium chloride powder in batches, reacted, standing still, washed with potassium sulfate solution for several times, washed with 2,2,5-trimethylhexane solution for several times, washed with the dodecane solution for several times, recrystallized in a diethylene glycol monoethyl ether solution, dehydrated with dehydrating agent, got 15 the finished product 4-benzyloxy-3-methoxy-4'-methylbenzophenone.
Description
The present invention discloses drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, comprises the following steps:2-bromo-3-methoxy-4-benzyloxy-4'-methyl diphenyl ether, sodium bromide solution were added to the reaction vessel, controlled the stirring rate, raised the solution temperature, reacted; then added the benzyl phthalate solution, added palladium chloride powder in batches, reacted, standing still, washed with potassium sulfate solution for several times, washed with 2,2,5-trimethylhexane solution for several times, washed with the dodecane solution for several times, recrystallized in a diethylene glycol monoethyl ether solution, dehydrated with dehydrating agent, got the finished product 4-benzyloxy-3-methoxy-4'-methylbenzophenone.
2018100827 19 Jun 2018
Drug intermediates 4-benzyloxy-3-methoxy-4’-methylbenzophenone synthesis method
FIELD OF THE INVENTION
The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method.
GENERAL BACKGROUND
4-benzyloxy-3-methoxy-4'-methylbenzophenone is a kind of synthesis intermediates, it is used for the production of anti-parkinson's disease drug tokamycin. procainamide However, most of the existing synthesis methods are using a mixture of hydrochloric acid, chromium oxide and pyridine constitutes a reactant. In this method of production, the chromium oxide will lead to higher post-reaction pollution treatment costs, hydrochloric acid’s volatility and corrosivity will lead to higher anticorrosion requirements for equipment, equipment maintenance costs is higher, it is not conducive to lower production costs, the synthesis method is complicated. Therefore, it is necessary to propose a new synthetic method.
SUMMARY
Based on the technical problems of the background technology, the purpose of the present invention is to provide drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, comprises the following steps:
A: 2-bromo-3-methoxy-4-benzyloxy-4'-methyl diphenyl ether, 2.3 L sodium bromide solution were added to the reaction vessel, controlled the stirring rate at 310-350 rpm, raised the solution temperature to 40-45 °C, reacted for 1-2 h;
B: then added the benzyl phthalate solution, added palladium chloride powder in 30 40 min in batches, reacted for 60-90 min, standing still for 2-3 h, washed with
2018100827 19 Jun 2018 potassium sulfate solution for several times, washed with 2,2,5-trimethylhexane solution for several times, washed with the dodecane solution for several times, recrystallized in a diethylene glycol monoethyl ether solution, dehydrated with dehydrating agent, got the finished product
4-benzyloxy-3-methoxy-4'-methylbenzophenone.
Preferably, the sodium bromide solution has a mass fraction of 10-16%. Preferably, the mass fraction of the benzyl phthalate solution is 30-35%. Preferably, the potassium sulfate solution has a mass fraction of 15-22%. Preferably, the 2,2,5-trimethylhexane solution has a mass fraction of 40-46%.
Preferably, the mass fraction of dodecane solution is 60-65%.
Preferably, the mass fraction of diethylene glycol monoethyl ether solution is
80-86%.
Preferably, the dehydrating agent is any one of anhydrous magnesium sulfate and activated alumina.
Throughout the reaction process can be the following reaction formula:
+ ^Η18Ο4 + Ci.PC
w h3co CH2°--1 //
CH
Compared with the synthetic method disclosed in the background art, the invention provides drug intermediates
4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, it is unnecessary to use the mixture of hydrochloric acid, chromium oxide and pyridine as reactants, avoiding the existence of chromium oxide that lead to the pollution to environment, avoiding the volatility and corrosivity of hydrochloric acid, reducing equipment maintenance costs, it is conducive to lower production costs, and reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good
2018100827 19 Jun 2018 foundation for further enhancing the yield of the reaction.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present 5 invention are further illustrated:
Embodiment 1
Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, comprises the following steps:
A: 2mol 2-bromo-3-methoxy-4-benzyloxy-4'-methyl diphenyl ether, 2.3 L sodium bromide solution with a mass fraction of 10% were added to the reaction vessel, controlled the stirring rate at 310 rpm, raised the solution temperature to 40 °C, reacted for 1 h;
B: then added the 4mol benzyl phthalate solution with a mass fraction of 30%, added 2mol palladium chloride powder in 40 min for 2 times, reacted for 60 min, standing still for 2 h, washed with potassium sulfate solution with a mass fraction of 15% for 5 times, washed with 2,2,5-trimethylhexane solution with a mass fraction of 40% for 3 times, washed with the dodecane solution with a mass fraction of 60% for 2 times, recrystallized in a diethylene glycol monoethyl ether solution with a mass fraction of 80%, dehydrated with anhydrous magnesium sulfatede hydrating agent, got the finished product 4-benzyloxy-3-methoxy-4'-methylbenzophenone 412.96g, yield 89%.
Embodiment 2
Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, comprises the following steps:
A: 2mol 2-bromo-3-methoxy-4-benzyloxy-4'-methyl diphenyl ether, 2.3 L sodium bromide solution with a mass fraction of 14% were added to the reaction vessel, controlled the stirring rate at 340 rpm, raised the solution temperature to 43 °C, reacted for 1.5 h;
B: then added the 4.5mol benzyl phthalate solution with a mass fraction of 32%, added 2.6mol palladium chloride powder in 40 min for 3 times, reacted for 75 min, standing still for 2.2 h, washed with potassium sulfate solution with a mass fraction of
2018100827 19 Jun 2018
18% for 6 times, washed with 2,2,5-trimethylhexane solution with a mass fraction of 44% for 4 times, washed with the dodecane solution with a mass fraction of 63% for 3 times, recrystallized in a diethylene glycol monoethyl ether solution with a mass fraction of 84%, dehydrated with activated alumina hydrating agent, got the finished product 4-benzyloxy-3-methoxy-4'-methylbenzophenone 426.88g, yield 92%. Embodiment 3
Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, comprises the following steps:
A: 2mol 2-bromo-3-methoxy-4-benzyloxy-4'-methyl diphenyl ether, 2.3 L sodium bromide solution with a mass fraction of 16% were added to the reaction vessel, controlled the stirring rate at 350 rpm, raised the solution temperature to 43 °C, reacted for 2 h;
B: then added the 5mol benzyl phthalate solution with a mass fraction of 35%, added 3mol palladium chloride powder in 40 min for 4 times, reacted for 90 min, standing still for 3 h, washed with potassium sulfate solution with a mass fraction of 22% for 7 times, washed with 2,2,5-trimethylhexane solution with a mass fraction of 46% for 5 times, washed with the dodecane solution with a mass fraction of 65% for 4 times, recrystallized in a diethylene glycol monoethyl ether solution with a mass fraction of 86%, dehydrated with anhydrous magnesium sulfatede hydrating agent, got the finished product 4-benzyloxy-3-methoxy-4'-methylbenzophenone 445.44g,yield 96%.
The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.
2018100827 19 Jun 2018
Claims (4)
- Claims1. Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method, comprises the following steps:5 A: 2-bromo-3-methoxy-4-benzyloxy-4'-methyl diphenyl ether, 2.3 L sodium bromide solution were added to the reaction vessel, controlled the stirring rate at 310-350 rpm, raised the solution temperature to 40-45 °C, reacted for 1-2 h;B: then added the benzyl phthalate solution, added palladium chloride powder in 40 min in batches, reacted for 60-90 min, standing still for 2-3 h, washed with10 potassium sulfate solution for several times, washed with 2,2,5-trimethylhexane solution for several times, washed with the dodecane solution for several times, recrystallized in a diethylene glycol monoethyl ether solution, dehydrated with dehydrating agent, got the finished product4-benzyloxy-3-methoxy-4'-methylbenzophenone.
- 2. Drug intermediates 4-benzyloxy-
- 3-methoxy-4'-methylbenzophenone synthesis method according to claim 1 wherein the sodium bromide solution has a mass fraction of 10-16%.20 3. Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method according to claim 1 wherein the mass fraction of the benzyl phthalate solution is 30-35%.
- 4. Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis25 method according to claim 1 wherein the potassium sulfate solution has a mass fraction of 15-22%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2017105289929 | 2017-07-01 | ||
| CN201710528992.9A CN108238869A (en) | 2017-07-01 | 2017-07-01 | - 4 ＇ of pharmaceutical intermediate 4- benzyloxy -3- methoxyl groups-methyldiphenyl ketone synthetic method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100827A4 true AU2018100827A4 (en) | 2018-08-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100827A Ceased AU2018100827A4 (en) | 2017-07-01 | 2018-06-19 | Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238869A (en) |
| AU (1) | AU2018100827A4 (en) |
| GB (1) | GB201713409D0 (en) |
| IE (1) | IES20180187A2 (en) |
-
2017
- 2017-07-01 CN CN201710528992.9A patent/CN108238869A/en active Pending
- 2017-08-21 GB GBGB1713409.9A patent/GB201713409D0/en not_active Ceased
-
2018
- 2018-06-19 AU AU2018100827A patent/AU2018100827A4/en not_active Ceased
- 2018-06-26 IE IES20180187 patent/IES20180187A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| GB201713409D0 (en) | 2017-10-04 |
| CN108238869A (en) | 2018-07-03 |
| IES20180187A2 (en) | 2019-11-13 |
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