CN106365998A - Preparation method of iodomethyl pivalate - Google Patents
Preparation method of iodomethyl pivalate Download PDFInfo
- Publication number
- CN106365998A CN106365998A CN201610688642.4A CN201610688642A CN106365998A CN 106365998 A CN106365998 A CN 106365998A CN 201610688642 A CN201610688642 A CN 201610688642A CN 106365998 A CN106365998 A CN 106365998A
- Authority
- CN
- China
- Prior art keywords
- preparation
- pivalate
- sodium iodide
- calcium chloride
- iodomethyl pivalate
- 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.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/287—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
Abstract
The invention discloses a preparation method of iodomethyl pivalate as an important medicine intermediate. The preparation method is characterized in that iodomethyl pivalate as a raw material and sodium iodide undergo a replacement reaction in ethyl acetate as a solvent under the condition of reaction backflow time of 6h. Compared with other synthesis methods, the preparation method of iodomethyl pivalate has a high mole yield. The iodomethyl pivalate obtained by the preparation method has product purity (GC) of 98% and thus the product has advantages in cost and purity.
Description
Technical field
The invention belongs to pharmaceutical intermediate technical field is and in particular to a kind of preparation method of iodometyl pivalate.
Background technology
Iodometyl pivalate, also known as trimethylacetic acid iodine methyl ester, neopentanoic acid iodine methyl ester, PA iodo methyl ester；One
Plant important medicine intermediate, the synthesis for follow-up product (Method of cefcapene pivoxil and Cefditoren pivoxil Cephalosporins) provides guarantee.
At present, the preparation of iodometyl pivalate is to make solvent with acetone mostly, with the direct substitution method of sodium iodide, document
Report purity and yield are all very high, but actually seldom can reach.
Content of the invention
The invention provides a kind of yield is more than the preparation method of 90% iodometyl pivalate, solve prior art system
Standby iodometyl pivalate purity is low, the low problem of yield, is that quality and the cost of subsequent product provides guarantee.
The present invention employs the following technical solutions:
A kind of preparation method of iodometyl pivalate it is characterised in that: with chloromethyl pivalate as raw material, take with sodium iodide
Generation reaction is obtained；Solvent in described substitution reaction is ethyl acetate；Reacting reflux time 6h.
The chemical formula of above-mentioned synthesis is:
1mol 1.2~1.5mol
Further, also need in described reaction to add calcium chloride, for control process moisture.
Further, take chloromethyl pivalate, ethyl acetate is solvent, sodium iodide and calcium chloride, is warming up to 78 DEG C of backflows
After 6h, it is cooled to 0 DEG C, is then washed till with 5% sodium thiosulfate colourless, anhydrous magnesium sulfate is dried, concentrating under reduced pressure obtains final product.
Further, described chloromethyl pivalate: sodium iodide: the mol ratio of calcium chloride is 1:1.2 ~ 1.5:0.5 ~ 1.2.
, compared with other synthetic methods, molar yield is high for the synthetic method of iodometyl pivalate that the present invention provides；Additionally,
The product purity (gc) of the present invention can reach 98%, and the product that therefore the method provides has very excellent greatly in terms of cost and purity
Gesture.
Specific embodiment
To describe the present invention with reference to embodiment, but the scope of protection of present invention is not limited to reality
Apply the scope that example is stated.
Embodiment 1: the synthesis of iodometyl pivalate
Add chloromethyl pivalate 10.0g, ethyl acetate 30ml, sodium iodide 11.6g and calcium chloride 3.6g in there-necked flask, be warming up to
After 78 DEG C of backflow 6h, it is cooled to 0 DEG C, is then washed till with 5% sodium thiosulfate colourless, anhydrous magnesium sulfate is dried, concentrating under reduced pressure.?
It is iodometyl pivalate compound to 16g yellow liquid.
Reaction molar yield is 94%, gc:98%.
Embodiment 2: the synthesis of iodometyl pivalate
Add chloromethyl pivalate 10.0g, ethyl acetate 30ml, sodium iodide 13.4g and calcium chloride 4.6g in there-necked flask, be warming up to
After 78 DEG C of backflow 6h, it is cooled to 0 DEG C, is then washed till with 5% sodium thiosulfate colourless, anhydrous magnesium sulfate is dried, concentrating under reduced pressure.?
It is iodometyl pivalate compound to 16g yellow liquid.
Reaction molar yield is 90%, gc:97.5%.
The identification of product in embodiment 3 embodiment of the present invention 1
Authentication method: Brooker avance iii 400mhz superconduction nuclear magnetic resonance spectrometer
, 6.17(2h) h-nmr (cdcl3): 1.25(9h)
Analysis method: gc(gas chromatographic purity)；Shimadzu gc-2020
, compared with other synthetic methods, molar yield is high for the synthetic method of iodometyl pivalate that the present invention provides；Additionally, this
Bright product purity (gc) can reach 98%, and the product that therefore the method provides has great advantage in terms of cost and purity.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, although with reference to the foregoing embodiments
The present invention is described in detail, for a person skilled in the art, it still can be to foregoing embodiments institute
The technical scheme recorded is modified, or carries out equivalent to wherein some technical characteristics.All spirit in the present invention and
Within principle, any modification, equivalent substitution and improvement made etc., should be included within the scope of the present invention.
Claims (6)
1. a kind of preparation method of iodometyl pivalate it is characterised in that: with chloromethyl pivalate as raw material, with sodium iodide occur
Substitution reaction is obtained.
2. preparation method according to claim 1 it is characterised in that: described reaction in solvent be ethyl acetate.
3. preparation method according to claim 1 it is characterised in that: described reaction in also need add calcium chloride.
4. preparation method according to claim 1 it is characterised in that: described reacting reflux time 6h.
5. the preparation method according to claim 1-3 it is characterised in that: described chloromethyl pivalate: sodium iodide: calcium chloride
Mol ratio be 1:1.2 ~ 1.5:0.5 ~ 1.2.
6. preparation method according to claim 5 it is characterised in that: take chloromethyl pivalate 10g, ethyl acetate 30ml,
Sodium iodide 11.6g and calcium chloride 3.6g, after being warming up to 78 DEG C of backflow 6h, is cooled to 0 DEG C, is then washed till no with 5% sodium thiosulfate
Color, anhydrous magnesium sulfate is dried, and concentrating under reduced pressure obtains final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610688642.4A CN106365998A (en) | 2016-08-19 | 2016-08-19 | Preparation method of iodomethyl pivalate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610688642.4A CN106365998A (en) | 2016-08-19 | 2016-08-19 | Preparation method of iodomethyl pivalate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106365998A true CN106365998A (en) | 2017-02-01 |
Family
ID=57878856
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610688642.4A Pending CN106365998A (en) | 2016-08-19 | 2016-08-19 | Preparation method of iodomethyl pivalate |
Country Status (1)
| Country | Link |
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| CN (1) | CN106365998A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107422056A (en) * | 2017-08-17 | 2017-12-01 | 山东裕欣药业有限公司 | A kind of gas-chromatography detection method of iodometyl pivalate and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992017185A1 (en) * | 1991-03-29 | 1992-10-15 | University Of Florida | Targeted drug delivery via mixed phosphate derivatives |
| WO2005009471A1 (en) * | 2003-07-28 | 2005-02-03 | Osaka Industrial Promotion Organization | Composition for lowering blood-sugar level |
| CN105764909A (en) * | 2013-11-04 | 2016-07-13 | 阿西耶斯生物公司 | Stable pantetheine derivatives for the treatment of pantothenate kinase associated neurodegeneration (PKAN) and methods for the synthesis of such compounds |
-
2016
- 2016-08-19 CN CN201610688642.4A patent/CN106365998A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992017185A1 (en) * | 1991-03-29 | 1992-10-15 | University Of Florida | Targeted drug delivery via mixed phosphate derivatives |
| WO2005009471A1 (en) * | 2003-07-28 | 2005-02-03 | Osaka Industrial Promotion Organization | Composition for lowering blood-sugar level |
| CN105764909A (en) * | 2013-11-04 | 2016-07-13 | 阿西耶斯生物公司 | Stable pantetheine derivatives for the treatment of pantothenate kinase associated neurodegeneration (PKAN) and methods for the synthesis of such compounds |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107422056A (en) * | 2017-08-17 | 2017-12-01 | 山东裕欣药业有限公司 | A kind of gas-chromatography detection method of iodometyl pivalate and preparation method thereof |
| CN107422056B (en) * | 2017-08-17 | 2020-04-24 | 山东裕欣药业有限公司 | Gas chromatography detection method of iodomethyl pivalate and preparation method thereof |
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| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170201 |