CN103130685A - Preparing method of (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate - Google Patents
Preparing method of (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate Download PDFInfo
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- CN103130685A CN103130685A CN2011103907214A CN201110390721A CN103130685A CN 103130685 A CN103130685 A CN 103130685A CN 2011103907214 A CN2011103907214 A CN 2011103907214A CN 201110390721 A CN201110390721 A CN 201110390721A CN 103130685 A CN103130685 A CN 103130685A
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- dimethyl
- cyclohexyl
- oxygen
- benzyl formate
- amino benzyl
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Abstract
The invention relates to a preparing method of (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate. The preparing method mainly solves the technical problems that in an existing synthetic process, the route is long, cost is high, reaction is not easy to control, experimental operation is inconvenient, and the like. According to the preparing method, 4,4-dimethyl-2-cyclohexene-1-ketone and amino benzyl formate are used as raw material, boron trifluoride diethyl etherate and tetrabutyl cetyltrimethylammonium bromide are used for catalysis, dichloromethane is used as solvent, and then the (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate is prepared at a normal temperature. The (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate is a key intermediate of the novel anti-cancer drug paclitaxel and derivatives thereof.
Description
Technical field
The present invention relates to the synthetic method of (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate.
Background technology
(2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate is as the key intermediate of new type anticancer medicine taxol and derivative thereof, its synthetic extensive concern that is subject to.The synthetic method of (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate [Canadian chemical journal (Canadian Journal of Chemistry at present; 2000; 925-934)] be mainly by by 4,4-dimethyl-2-tetrahydrobenzene-1-ketone first with the potassium cyanide addition, the protection carbonyl, then half hydrolysis, hofmann rearrangement goes the reaction such as protection to obtain (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate.This synthetic method needed for six steps just can obtain product altogether, and mainly there is following problem in it: will use highly toxic product potassium cyanide and hazardous substance bromine in (1) reaction process, the dangerous inconvenience of experimental implementation; (2) testing sequence is long, and process of the test is loaded down with trivial details, and cost is high.Concrete reaction formula is as follows:
Therefore, need raw material of exploitation to be easy to get, easy to operate, reaction is easy to control, the synthetic method that cost is low.
Summary of the invention
The objective of the invention is to develop and a kind ofly have raw material and be easy to get, easy to operate, reaction is easy to control, the preparation method of (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate that cost is low.Mainly solve present synthetic route long, use hypertoxic raw material, operation inconvenience, high in cost of production technical problem.
Technical scheme of the present invention: the present invention is with 4,4-dimethyl-2-tetrahydrobenzene-1-ketone and benzyl carbamate are as reactant, and under boron trifluoride diethyl etherate and four butyl bromation amine catalysis, methylene dichloride is made solvent, preparation (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate under normal temperature.Reaction formula is as follows:
Beneficial effect of the present invention: the invention solves in the synthesis technique of both having known at present route long, cost is high, reacts loaded down with trivial details, the shortcomings such as experimental implementation inconvenience.Adopt new synthetic method only to need one-step synthesis, greatly shortened synthetic route, reduced cost and be easy to and amplified, can realize 4,4-dimethyl-2-tetrahydrobenzene-1-ketone and the quick preparation in benzyl carbamate laboratory and industrial large-scale production.
Embodiment
Embodiment 1:
With 4 of 0.25 g (0.002 mol), 4-dimethyl-2-tetrahydrobenzene-1-ketone and benzyl carbamate 0.4 ml (0.0024 mol) are dissolved in 10 ml anhydrous methylene chlorides, then the four butyl bromation amine that adds successively 0.06 g (0.0002 mol), boron trifluoride diethyl etherate 0.284 g (0.056 mol), the stirring at normal temperature reaction is spent the night.Thin layer chromatography detects raw material and disappears, the reaction solution removal of solvent under reduced pressure, and resistates is through preparation plate (ethyl acetate: sherwood oil, V:V=1: 2) obtain (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate 0.09 g, yield: 16.3%.
Embodiment 2:
With 4 of 1.24 g (0.01 mol), 4-dimethyl-2-tetrahydrobenzene-1-ketone and benzyl carbamate 2.01 ml (0.012 mol) are dissolved in the methylene dichloride of 20 mL, then the four butyl bromation amine that adds successively 0.322 g (0.001 mol), boron trifluoride diethyl etherate 0.284 g (0.002 mol), the stirring at normal temperature reaction is spent the night.Thin layer chromatography detects raw material and disappears, reaction solution washs with saturated sodium bicarbonate solution 1 L, organic phase is separated, anhydrous sodium sulfate drying, removal of solvent under reduced pressure, resistates is through column chromatography (ethyl acetate: sherwood oil, V:V=1: 30 to 1: 4) obtain crude product, obtain (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate 0.58 g, yield: 21.1% after using re-crystallizing in ethyl acetate.
Embodiment 3:
With 4 of 14.7 g (0.1185 mol), 4-dimethyl-2-tetrahydrobenzene-1-ketone and benzyl carbamate 21.43 ml (0.142 mol) are dissolved in the methylene dichloride of 2 L, then the four butyl bromation amine that adds successively 3.45 g (0.0118 mol), boron trifluoride diethyl etherate 3.36 g (0.0237 mol), the stirring at normal temperature reaction is spent the night.Thin layer chromatography detects raw material and disappears, reaction solution washs with saturated sodium bicarbonate solution 1 L, organic phase is separated, anhydrous sodium sulfate drying, removal of solvent under reduced pressure, resistates is through column chromatography (ethyl acetate: sherwood oil, V:V=1: 30 to 1: 4) obtain crude product, obtain (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate 8.66 g, yield: 26.6% after using re-crystallizing in ethyl acetate.
Claims (1)
1. one kind (2, the preparation method of 2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate, it is characterized in that comprising the following steps: with 4,4-dimethyl-2-tetrahydrobenzene-1-ketone and benzyl carbamate are raw material, under boron trifluoride diethyl etherate and four butyl bromation amine catalysis, methylene dichloride is made solvent, and under normal temperature, reaction obtains (2,2-dimethyl-5-oxygen-cyclohexyl)-benzyl carbamate, reaction formula is as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103907214A CN103130685A (en) | 2011-12-01 | 2011-12-01 | Preparing method of (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate |
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| CN2011103907214A CN103130685A (en) | 2011-12-01 | 2011-12-01 | Preparing method of (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate |
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| CN103130685A true CN103130685A (en) | 2013-06-05 |
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| CN2011103907214A Pending CN103130685A (en) | 2011-12-01 | 2011-12-01 | Preparing method of (2,2-dimethyl-5-oxygen-cyclohexyl)-amino benzyl formate |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101068801A (en) * | 2004-10-14 | 2007-11-07 | 艾博特股份有限两合公司 | Arylsulfonylmethyl or arylsulfonamide substituted aromatic compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor |
| WO2008060488A1 (en) * | 2006-11-14 | 2008-05-22 | Merck & Co., Inc. | Tricyclic heteroaromatic compounds as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
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2011
- 2011-12-01 CN CN2011103907214A patent/CN103130685A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101068801A (en) * | 2004-10-14 | 2007-11-07 | 艾博特股份有限两合公司 | Arylsulfonylmethyl or arylsulfonamide substituted aromatic compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor |
| WO2008060488A1 (en) * | 2006-11-14 | 2008-05-22 | Merck & Co., Inc. | Tricyclic heteroaromatic compounds as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
Non-Patent Citations (1)
| Title |
|---|
| XU LI-WEN等: ""Highly Efficient Aza-Michael Reactions of Enones with Carbamates Using a Combination of Quaternary Ammonium Salts and BF3OEt2 as a Catalyst"", 《SYNLETT》 * |
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Application publication date: 20130605 |