AU2018100396A4 - Medicine intermediates 2,4-difluorobenzoic acid synthesis method - Google Patents
Medicine intermediates 2,4-difluorobenzoic acid synthesis method Download PDFInfo
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- AU2018100396A4 AU2018100396A4 AU2018100396A AU2018100396A AU2018100396A4 AU 2018100396 A4 AU2018100396 A4 AU 2018100396A4 AU 2018100396 A AU2018100396 A AU 2018100396A AU 2018100396 A AU2018100396 A AU 2018100396A AU 2018100396 A4 AU2018100396 A4 AU 2018100396A4
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- difluorobenzoic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
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- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Abstract Medicine intermediates 2,4-difluorobenzoic acid synthesis method, comprises the following steps: the reaction vessel was added 3-4 mol 1,3-dichloro-2-propanol 5 solution, 2 mol 2,4-difluoro-6-bromo-isopropylbenzene solution, 600-800 mL aqueous solution, controlled stirring speed at 110 -130rpm, raised the temperature of the solution to 40-50 'C, added 5-6mol boron trifluoride ether solution, keep for 90-110min, after the end of the reaction, under vacuum concentration, added 300ml 1-pentanol solution, filtered, adjusted the pH of the filtrate to 4-5, after the crystals are 10 precipitated, filtered and recrystallized in the 4-methyl-2-pentanone solution, and dehydrated with the dehydrating agent to obtain the product 2,4-difluorobenzoic acid.
Description
FIELD OF THE INVENTION
The present invention relates to medicine intermediates 2,4-difluorobenzoic acid 5 synthesis method.
GENERAL BACKGROUND
2,4-difluorobenzoic acid is an important intermediate for organic synthesis, it is mainly used in pharmaceutical intermediates, organic synthesis, organic solvents, it can also be used in dye production, pesticide production and spices and so on.
2.4- difluorobenzoic acid is generally prepared from 5-step reaction by reduction, diazotization, fluorination, acylation and oxidation. The reaction step is long and the diazotization reaction needs to be controlled at low temperature, the operation is difficult, the yield is low, the process is more complex. Therefore, it is necessary to propose a new synthetic method for further improving the quality and yield of the product and reducing the byproduct content, it has important economic significance.
SUMMARY
The purpose of the present invention is to provide medicine intermediates
2,4-difluorobenzoic acid synthesis method, comprises the following steps:
(i) the reaction vessel was added 3-4 mol l,3-dichloro-2-propanol solution, 2 mol
2.4- difluoro-6-bromo-isopropylbenzene solution, 600-800 mL aqueous solution, controlled stirring speed at 110 -130rpm, raised the temperature of the solution to 40-50 °C, added 5-6mol boron trifluoride ether solution, keep for 90-110min, after the end of the reaction, under vacuum concentration, added 300ml 1-pentanol solution, filtered, adjusted the pH of the filtrate to 4-5, after the crystals are precipitated, filtered and recrystallized in the 4-methyl-2-pentanone solution, and dehydrated with the dehydrating agent to obtain the product 2,4-difluorobenzoic acid; wherein, , the mass fraction of l,3-dichloro-2-propanol described in step (i) is 60-70%, and the mass fraction of 2,4-difluoro-6-bromo-isopropylbenzene described in step (i) is 90-93%, the
2018100396 29 Mar 2018 mass fraction of the boron trifluoride butyl ether solution in step (i) is 80-85%, the mass fraction of the 1-pentanol solution in step (i) is 86-90%, the mass fraction of the 4-methyl-2-pentanone in step (i) is 91-95%, and the dehydrating agent described in step (i) is any one of anhydrous sodium sulfate and phosphorus pentoxide.
Throughout the reaction process can be the following reaction formula:
Advantage of the present invention is that: reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
medicine intermediates 2,4-difluorobenzoic acid synthesis method.
Embodiment 1
The reaction vessel was added 3 mol l,3-dichloro-2-propanol solution with a mass fraction of 60%, 2 mol 2,4-difluoro-6-bromo-isopropylbenzene solution with a mass fraction of 90%, 600 mL water solution, controlled the stirring speed at 110 rpm, increased the solution temperature to 40 °C, added 5 mol boron trifluoride butyl ether solution with a mass fraction of 80%, keep for 90 min, after the end of the reaction, under vacuum concentration, added 300mL 1-pentanol solution with a mass fraction 86%, filtered, the pH of the filtrate was adjusted to 4, precipitated crystals, filtered, recrystallized in 4-methyl-2-pentanone solution with a mass fraction of 91%, dehydrated with anhydrous sodium sulfate dehydrating agent, finally get the product
2,4-difluorobenzoic acid 290.72g, the yield of 92%.
2018100396 29 Mar 2018
Embodiment 2
The reaction vessel was added 3.5 mol l,3-dichloro-2-propanol solution with a mass fraction of 65%, 2 mol 2,4-difluoro-6-bromo-isopropylbenzene solution with a mass fraction of 91%, 700 mL water solution, controlled the stirring speed at 120 rpm, increased the solution temperature to 45 °C, added 5.5 mol boron trifluoride butyl ether solution with a mass fraction of 82%, keep for 100 min, after the end of the reaction, under vacuum concentration, added 300mL 1-pentanol solution with a mass fraction 88%, filtered, the pH of the filtrate was adjusted to 4.5, precipitated crystals, filtered, recrystallized in 4-methyl-2-pentanone solution with a mass fraction of 93%, dehydrated with phosphorus pentoxide dehydration, finally get 2,4-difluorobenzoic acid 297.04g, yield 94%.s
Embodiment 3
The reaction vessel was added 4mol l,3-dichloro-2-propanol solution with a mass 15 fraction of 70%, 2 mol 2,4-difluoro-6-bromo-isopropylbenzene solution with a mass fraction of 93%, 800 mL water solution, controlled the stirring speed at 130 rpm, increased the solution temperature to 50 °C, added 6 mol boron trifluoride butyl ether solution with a mass fraction of 85%, keep for 110 min, after the end of the reaction, under vacuum concentration, added 300mL 1-pentanol solution with a mass fraction
90%, filtered, the pH of the filtrate was adjusted to 5, precipitated crystals, filtered, recrystallized in 4-methyl-2-pentanone solution with a mass fraction of 95%, dehydrated with anhydrous sodium sulfate dehydrating agent, finally get the product
2,4-difluorobenzoic acid 306.52g, the yield of 97%.
2018100396 29 Mar 2018
Claims (3)
1. Medicine intermediates 2,4-difluorobenzoic acid synthesis method, comprises the following steps:
(i) the reaction vessel was added 3-4 mol l,3-dichloro-2-propanol solution, 2 mol 5 2,4-difluoro-6-bromo-isopropylbenzene solution, 600-800 mL aqueous solution, controlled stirring speed at 110 -130rpm, raised the temperature of the solution to 40-50 °C, added 5-6mol boron trifluoride ether solution, keep for 90-110min, after the end of the reaction, under vacuum concentration, added 300ml 1-pentanol solution, filtered, adjusted the pH of the filtrate to 4-5, after the crystals are precipitated,
10 filtered and recrystallized in the 4-methyl-2-pentanone solution, and dehydrated with the dehydrating agent to obtain the product 2,4-difluorobenzoic acid; wherein, , the mass fraction of l,3-dichloro-2-propanol described in step (i) is 60-70%, and the mass fraction of 2,4-difluoro-6-bromo-isopropylbenzene described in step (i) is 90-93%, the mass fraction of the boron trifluoride butyl ether solution in step (i) is 80-85%, the
15 mass fraction of the 1-pentanol solution in step (i) is 86-90%.
2. Medicine intermediates 2,4-difluorobenzoic acid synthesis method according to claim 1 wherein the mass fraction of the 4-methyl-2-pentanone in step (i) is 91-95%.
3. Medicine intermediates 2,4-difluorobenzoic acid synthesis method according to claim 1 wherein the dehydrating agent described in step (i) is any one of anhydrous sodium sulfate and phosphorus pentoxide.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710155464.3A CN108623447A (en) | 2017-03-19 | 2017-03-19 | A kind of synthetic method of medicine intermediate 2,4 difluorobenzene formic acid |
| GBGB1705499.0 | 2017-04-05 | ||
| GBGB1705499.0A GB201705499D0 (en) | 2017-03-19 | 2017-04-05 | Medicine intermediates 2,4-difluorobenzoic acid synthesis method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100396A4 true AU2018100396A4 (en) | 2018-05-17 |
Family
ID=58682515
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100396A Ceased AU2018100396A4 (en) | 2017-03-19 | 2018-03-29 | Medicine intermediates 2,4-difluorobenzoic acid synthesis method |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN108623447A (en) |
| AU (1) | AU2018100396A4 (en) |
| GB (1) | GB201705499D0 (en) |
-
2017
- 2017-03-19 CN CN201710155464.3A patent/CN108623447A/en active Pending
- 2017-04-05 GB GBGB1705499.0A patent/GB201705499D0/en not_active Ceased
-
2018
- 2018-03-29 AU AU2018100396A patent/AU2018100396A4/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| GB201705499D0 (en) | 2017-05-17 |
| CN108623447A (en) | 2018-10-09 |
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| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |