CN103242276B - Synthesis method of 2, 2-dimethyltetrahydro-2H-pyran-4-carboxylic acid - Google Patents
Synthesis method of 2, 2-dimethyltetrahydro-2H-pyran-4-carboxylic acid Download PDFInfo
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Abstract
The invention discloses a synthesis method of 2, 2-dimethyltetrahydro-2H-pyran-4-carboxylic acid, belonging to the field of chemical synthesis. According to the synthesis method disclosed by the invention, ethyl bromide is taken as a starting raw material, and a required compound is simply and conveniently synthesized through Sonogashira coupling reaction, Kucherov reaction, Darzen reaction, oxidation reaction and other steps. The synthesis method has the advantages of simple synthesis process, low raw material price, easiness in obtaining the raw material, mild reaction conditions, low cost, high yield, good reaction environment and easiness in industrial production.
Description
Technical field
The invention belongs to chemosynthesis technical field, relate to a kind of compound 2, the synthetic method of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid.
Background technology
2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid is a kind of important medicine intermediate, is the important synthesis material of a lot of medicines and auxiliary.The synthetic of the preparations such as such as PDE9 inhibitor, VAP-1 inhibitor, mTOR kinase inhibitor, NK-3 receptor antagonist is all applied to 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid.In the last few years, be a series ofly found with the synthetic pharmaceutical activity group of 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, the demand to such intermediate on market increases day by day.The structural formula of 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid is as follows:
At present, synthetic 2, the technique circuit of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid mainly contains following three kinds: the first is taking ether as solvent, under sodium hydride effect, taking mesityl oxide and ethyl formate as starting raw material, reaction generates 1-hydroxy-5-methyl base-1, 4-hexadiene-3-ketone, 1-hydroxy-5-methyl base-1, 4-hexadiene-3-ketone obtains 2 at palladium catalysis ShiShimonoseki ring, 3-dihydro-2, 2-dimethyl-4H-pyrans-4-ketone, through palladium catalytic hydrogenating reduction, reaction obtains 2, 2-dimethyl tetrahydro pyrans-4-one, 2, 2-dimethyl tetrahydro pyrans-4-one and Methyl benzenesulfonyl methyl isonitrile reaction is made to tetrahydrochysene-2, 2-dimethyl-2H-pyrans-4-formonitrile HCN, obtain target product 2 through hydrolysis reaction again, 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid (specifically seeing patent WO2006058723).Total recovery is lower than 20%.Its synthetic route is as follows.
The second synthetic method, taking 3-methyl-2-butene aldehyde as starting raw material, taking tetrahydrofuran (THF) as solvent, at subzero 78 DEG C, with ethynyl bromination reactive magnesium, obtain 5-methyl-4-hexene-1-alkynes-3-alcohol, 5-methyl-4-hexene-1-alkynes-3-alcohol again through Kucherov react 2, 2-dimethyl tetrahydro pyrans-4-one, 2, 2-dimethyl tetrahydro pyrans-4-one and Methyl benzenesulfonyl methyl isonitrile reaction is made to tetrahydrochysene-2, 2-dimethyl-2H-pyrans-4-formonitrile HCN, obtain target product 2 through hydrolysis reaction again, 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, total recovery is specifically shown in WO2004058763 lower than 25%().Its synthetic route is as follows:
All there is following shortcoming in above-mentioned two kinds of methods: (1) raw material costliness, and cost is high; (2) use ether as solvent, be unfavorable for environment and suitability for industrialized production, and cost recovery is high; (3) complicated operation, yield is low.(4) condition harshness, higher to equipment requirements.Therefore, low cost, high-level efficiency, synthetic 2, the 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid of high yield have very important industrial significance.
Summary of the invention
The object of the invention is for problems of the prior art, a kind of synthetic compound 2 is provided, the novel method of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid.
?the present invention synthetic 2, the method of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, be using bromine ethene etc. as starting raw material, by Yuan coupled reaction of Tong Guo, Kucherov reaction, reach the steps such as ginseng reaction and oxidizing reaction, synthesized simply and easily target compound.Specifically comprise following processing step:
(1) 2-methyl-5-hexene-3-alkynes-2-alcohol is synthetic
Under nitrogen protection, taking DMF or THF as solvent, taking palladium class catalyzer and metal halide as composite catalyst, under alkaline environment, make 2-methyl-3-butyne-2-alcohol and the bromine ethene mol ratio with 1.0:1.0 ~ 1.5:1.0, in-5 ~ 30 DEG C of reactions 8 ~ 15 hours; React rear extraction, 1 ~ 3M salt acid elution for organic phase, anhydrous sodium sulfate drying, filters, precipitation, underpressure distillation, obtains 2-methyl-5-hexene-3-alkynes-2-alcohol;
Described palladium class catalyzer is triphenylphosphine palladium chloride, four triphenyl phosphorus palladium or palladium; Palladium class catalyst levels be 2-methyl-3-butyne-2-alcohol molar weight 0.02 ~ 0.5%;
Described catalyst metal halogenide is cuprous chloride, cuprous bromide or cuprous iodide, its consumption be 2-methyl-3-butyne-2-alcohol molar weight 0. 5 ~ 1.2%;
Described alkali is triethylamine, at least one in diethylamine, pyridine, and the consumption of organic bases is 1 ~ 5 times of molar weight of 2-methyl-3-butyne-2-alcohol.
Synthesizing of (2) 2,2-dimethyl tetrahydro pyrans-4-one
Taking mercury salt and sulfuric acid as composite catalyst, make 2-methyl-5-hexene-3-alkynes-2-alcohol and water in 80 ~ 110 DEG C of addition reactions 10 ~ 15 hours; After reacting completely, be cooled to room temperature, adjust pH=7 ~ 9; Extraction, anhydrous sodium sulfate drying, filtration, precipitation, underpressure distillation, obtains product 2,2-dimethyl tetrahydro pyrans-4-one;
Described mercury salt is mercuric acetate or Mercury bisulfate, the amount of mercury salt be 2-methyl-5-hexene-3-alkynes-2-alcohol molar weight 1 ~ 6%;
The consumption of described sulfuric acid be 2-methyl-5-hexene-3-alkynes-2-alcohol molar weight 14 ~ 73%.
(3) 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester synthetic
Taking toluene as solvent, under alkali effect, 2,2-dimethyl tetrahydro pyrans-4-one and ethyl chloroacetate are with the mixed in molar ratio of 1:1 ~ 1:1.5, room temperature reaction 4 ~ 7 hours, add water and separate organic phase, organic phase washing, anhydrous sodium sulfate drying, precipitation, obtain 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester;
Described alkali is sodium amide, sodium ethylate, sodium methylate or the trimethyl carbinol; The consumption of alkali is 1 ~ 1.6 times of synthetic molar weight of 2-methyl-5-hexene-3-alkynes-2-alcohol.
(4) 2,2-dimethyl tetrahydro pyrans-4-formaldehyde are synthetic
By 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester and inorganic alkali solution are with the mixed in molar ratio of 1:1 ~ 1:1.5, and stirring at room temperature reaction 10 ~ 15 hours, is then warming up to 95 ~ 105 DEG C, add 1 ~ 3M hydrochloric acid to carry out acidolysis, collect the product of generation and the mixture of water, extraction, precipitation, obtain product 2,2-dimethyl tetrahydro pyrans-4-formaldehyde;
Described inorganic alkali solution is sodium hydroxide solution or the potassium hydroxide solution of mass concentration 10% ~ 35%.
Synthesizing of (5) 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acids
By soluble in water 2,2-dimethyl tetrahydro pyrans-4-formaldehyde, add oxygenant, stirring reaction 10 ~ 15 hours, filters, and filtrate adjusts pH to separating out solid, filters, and obtains target product 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid;
Described oxygenant is potassium permanganate, oxygen or hydrogen peroxide, and the consumption of oxygenant is 1 ~ 6 times of 2,2-dimethyl tetrahydro pyrans-4-formaldehyde molar weight.
The present invention 2, and the synthetic line of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid is as follows:
Synthetic product of the present invention is through proton nmr spectra, and high resolution gas chromatography is measured, and its finished product are 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, and purity is more than 98%, and yield is more than 50%.
The present invention is relative, and prior art has the following advantages:
1, the present invention, taking bromine ethene, alcohol as Yuan coupled reaction of starting raw material ， Jing, Kucherov react, reach ginseng reaction, oxidizing reaction, has synthesized target compound, its raw material is cheap and easy to get, and cost is low, and technique is simple, easy to operate, there is very important industrial significance;
2, the synthesis technique cycle of the present invention short, efficiency is high, yield is high.
Brief description of the drawings
Fig. 1 is the gas-chromatography of synthetic product of the present invention;
Fig. 2 is the synthetic nuclear magnetic spectrogram of the present invention.
Embodiment
Below by specific embodiment, synthetic method of the present invention is described further.
Embodiment 1
(1) 2-methyl-5-hexene-3-alkynes-2-alcohol is synthetic
Under nitrogen protection, in reaction flask, add the triethylamine of 1300mL, stir after 30min, be cooled to 0 DEG C with chilled brine, add 6.1 g(0.062mol) cuprous chloride and 7.0g(0.01mol) triphenylphosphine palladium chloride, stir after 20min, add 2-methyl-3-butyne-2-alcohol of 400mL, stir 30min, at 0 ~ 5 DEG C of THF solution 1050mL of bromine ethene that drips 5M, within 2 hours, drip off; Naturally be warming up to room temperature, stirring reaction 12 hours, GC monitoring has been reacted, the solid such as salt that filters out generation, filtrate decompression reclaims solvent, and residuum adds 200mL water, extract with ethyl acetate 3 × 100ml, ethyl acetate uses 2M hydrochloric acid 2 × 800mL to wash mutually, and anhydrous sodium sulfate drying filters, precipitation, underpressure distillation, obtains 2-methyl-5-hexene-3-alkynes-2-alcohol 390g, yield 86%.
Synthesizing of (2) 2,2-dimethyl tetrahydro pyrans-4-one
The aqueous sulfuric acid of 485mL 5% is joined in reactor, adds 31.8g(0.1mol) mercuric acetate and 195g(1.773mol) 2-methyl-5-hexene-3-alkynes-2-alcohol, be slowly heated to 95 DEG C, react 14 hours; Then be cooled to 0 DEG C of left and right, slowly adjust pH=7 ~ 8 with potassium hydroxide, with ethyl acetate 2 × 500mL extraction, merge organic phase, wash with 2 × 2000mL, 200g anhydrous sodium sulfate drying, filters out siccative, precipitation, oil pump underpressure distillation, obtain 2,2-dimethyl tetrahydro pyrans-4-one 202g, yield 89%.
(3) 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester synthetic
Get 47g(0.87mol) sodium methylate joins in the toluene of 300L, reflux half an hour, is down to room temperature; Slowly drip 110g(0.87mol) ethyl chloroacetate and 110g(0.86mol) 2,2-dimethyl tetrahydro pyrans-4-one, drips off for 4 hours; Slowly add the frozen water of 300mL, stir 0.5h; Separate organic phase, 3 × 200mL ethyl acetate extraction for water, combined ethyl acetate phase, with 2 × 100mL washing, anhydrous sodium sulfate drying, underpressure distillation, obtains 5,5-dimethyl-1, the synthetic 154g of 6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester, yield 84%.
What (4) 2,2-dimethyl tetrahydro pyrans-4-formaldehyde were synthetic synthesizes
Add 70mL water answering in still, add 28g(0.7mol) sodium hydroxide, stir 0.5h; Slowly add 150g(0.7mol) 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester, 30 DEG C are stirred 12h; The solid precipitation that adds the water dissolution reaction of 140mL to generate; Be warming up to 100 DEG C of left and right, drip the hydrochloric acid 700mL of 1M, the product that collection distills out simultaneously and the mixture of water, with the extraction of 3 × 200mL ethyl acetate, precipitation, obtain the synthetic 83.6g of 2,2-dimethyl tetrahydro pyrans-4-formaldehyde, yield 84%.
(5) 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acids are synthetic
By 54g(0.38mol) 2, in the water of 2-dimethyl tetrahydro pyrans-4-formaldehyde 500mL, add potassium permanganate 59g(0.38mol), room temperature reaction 12h, centrifuging, filtrate is adjusted pH=6 ~ 7 with concentrated hydrochloric acid, stir 2h, centrifuging obtains white solid end product 55.87g, yield 93%.The total recovery of end product is 50%.
Embodiment 2
(1) 2-methyl-5-hexene-3-alkynes-2-alcohol is synthetic
Under nitrogen protection, in reaction flask, add the diethylamine of 1300ml, stir after 30min, be cooled to 0 DEG C with chilled brine, add the cuprous iodide of 12g and the triphenylphosphine palladium chloride of 7.0g, stir after 20min, add 2-methyl-3-butyne-2-alcohol of 400ml, stir 30min, at 0 ~ 5 DEG C of THF solution 1050ml of bromine ethene that drips 5M, within 3 hours, drip off; Naturally be warming up to room temperature, stirring reaction 12 hours, GC monitoring has been reacted, the solid such as salt that filters out generation, filtrate decompression reclaims solvent, and residuum adds 200ml water, extract with ethyl acetate 3 × 100ml, ethyl acetate uses 2M hydrochloric acid 2 × 800ml to wash mutually, and anhydrous sodium sulfate drying filters, precipitation, underpressure distillation, obtains 2-methyl-5-hexene-3-alkynes-2-alcohol 399g, yield 88%.
Synthesizing of (2) 2,2-dimethyl tetrahydro pyrans-4-one: the aqueous sulfuric acid of 810ml 15% is joined in reactor, add Mercury bisulfate and the 195g2-methyl-5-hexene-3-alkynes-2-alcohol of 30.6g, be slowly heated to 95 DEG C, react 10 hours; Then be cooled to 0 DEG C of left and right, slowly adjust pH=7 ~ 8 with potassium hydroxide, with ethyl acetate 2 × 500ml extraction, merge organic phase, wash with 2 × 2000ml, 200g anhydrous sodium sulfate drying, filters out siccative, precipitation, oil pump underpressure distillation, obtain 2,2-dimethyl tetrahydro pyrans-4-one 193g, yield 85%.
(3) 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester synthetic: take in the toluene that 59g sodium ethylate joins 300L, reflux half an hour, be down to room temperature; Slowly drip 110g ethyl chloroacetate and 110g2,2-dimethyl tetrahydro pyrans-4-one, drips off for 6 hours; Slowly add the frozen water of 300ml, stir 0.5h; Separate organic phase, 3 × 200ml ethyl acetate extraction for water, combined ethyl acetate phase, with 2 × 100ml washing, anhydrous sodium sulfate drying, underpressure distillation, obtains 5,5-dimethyl-1, the synthetic 163g of 6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester, yield 89%.
What (4) 2,2-dimethyl tetrahydro pyrans-4-formaldehyde were synthetic synthesizes: in reactor, add 70ml water, add the sodium hydroxide of 42g, stir 0.5h; Slowly add 150g5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester, 30 DEG C are stirred 12h; The solid precipitation that adds the water dissolution reaction of 140ml to generate; Be warming up to 100 DEG C of left and right, drip the hydrochloric acid 1100ml of 1M, the product that collection distills out simultaneously and the mixture of water, with the extraction of 3 × 200ml ethyl acetate, precipitation, obtain the synthetic 84.6g of 2,2-dimethyl tetrahydro pyrans-4-formaldehyde, yield 85%.
(5) 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid is synthetic: by 2 of 54g, in the water of 2-dimethyl tetrahydro pyrans-4-formaldehyde 2000ml, add potassium permanganate 295g, room temperature reaction 13h, centrifuging, filtrate is adjusted pH=6-7 with concentrated hydrochloric acid, stir 2h, centrifuging obtains white solid end product 55.26g, yield 92%.The total recovery of end product is 52%.
Embodiment 3
(1) 2-methyl-5-hexene-3-alkynes-2-alcohol is synthetic
Under nitrogen protection, in reaction flask, add the triethylamine of 1300ml, stir after 30min, be cooled to 0 DEG C with chilled brine, add the cuprous iodide of 12g and 12g tetra-triphenylphosphine palladium, stir after 20min, add 2-methyl-3-butyne-2-alcohol of 400ml, stir 30min, at the 8-18 DEG C of THF solution 1050ml of bromine ethene that drips 5M, within 5 hours, drip off; Naturally be warming up to room temperature, stirring reaction 12 hours, GC monitoring has been reacted, the solid such as salt that filters out generation, filtrate decompression reclaims solvent, and residuum adds 200ml water, extract with ethyl acetate 3 × 100ml, ethyl acetate uses 2M hydrochloric acid 2 × 800ml to wash mutually, and anhydrous sodium sulfate drying filters, precipitation, underpressure distillation, obtains 2-methyl-5-hexene-3-alkynes-2-alcohol 399g, yield 88%.
Synthesizing of (2) 2,2-dimethyl tetrahydro pyrans-4-one: the aqueous sulfuric acid of 485ml 5% is joined in reactor, add Mercury bisulfate and the 195g2-methyl-5-hexene-3-alkynes-2-alcohol of 30.6g, be slowly heated to 95 DEG C, react 14 hours; Then be cooled to 0 DEG C of left and right, slowly adjust pH=7 ~ 8 with potassium hydroxide, with ethyl acetate 2 × 500ml extraction, merge organic phase, wash with 2 × 2000ml, 200g anhydrous sodium sulfate drying, filters out siccative, precipitation, oil pump underpressure distillation, obtain 2,2-dimethyl tetrahydro pyrans-4-one 192g, yield 85%.
(3) 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester synthetic: take in the toluene that 47g sodium methylate joins 300L, reflux half an hour, be down to room temperature; Slowly drip 110g ethyl chloroacetate and 110g2,2-dimethyl tetrahydro pyrans-4-one, drips off for 7 hours; Slowly add the frozen water of 300ml, stir 0.5h; Separate organic phase, 3 × 200ml ethyl acetate extraction for water, combined ethyl acetate phase, with 2 × 100ml washing, anhydrous sodium sulfate drying, underpressure distillation, obtains 5,5-dimethyl-1, the synthetic 157g of 6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester, yield 86%.
What (4) 2,2-dimethyl tetrahydro pyrans-4-formaldehyde were synthetic synthesizes: in reactor, add 70ml water, add the potassium hydroxide of 47g, stir 0.5h; Slowly add 150g5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester, 30 DEG C are stirred 12h; The solid precipitation that adds the water dissolution reaction of 140ml to generate; Be warming up to 100 DEG C of left and right, drip the hydrochloric acid 700ml of 1M, the product that collection distills out simultaneously and the mixture of water, with the extraction of 3 × 200ml ethyl acetate, precipitation, obtain the synthetic 84.6g of 2,2-dimethyl tetrahydro pyrans-4-formaldehyde, yield 85%.
(5) 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid is synthetic: by 2 of 54g, 2-dimethyl tetrahydro pyrans-4-formaldehyde is dissolved in the water of 1000ml, add potassium permanganate 168g, room temperature reaction 12h, centrifuging, filtrate is adjusted pH=6-7 with concentrated hydrochloric acid, stir 2h, centrifuging obtains white solid end product 56g, yield 94%.The total recovery of end product is 51%.
Claims (5)
- The synthetic method of 1.2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, comprises following processing step:(1) 2-methyl-5-hexene-3-alkynes-2-alcohol is synthetic: under nitrogen protection, taking DMF or THF as solvent, taking palladium class catalyzer and metal halide as composite catalyst, under alkaline environment, make 2-methyl-3-butyne-2-alcohol and the bromine ethene mol ratio with 1.0:1.0～1.5:1.0, in-5～30 DEG C of reactions 8～15 hours; React rear extraction, 1～3M salt acid elution for organic phase, anhydrous sodium sulfate drying, filters, precipitation, underpressure distillation, obtains 2-methyl-5-hexene-3-alkynes-2-alcohol;Described palladium class catalyzer is triphenylphosphine palladium chloride, tetra-triphenylphosphine palladium or palladium; Palladium class catalyst levels be 2-methyl-3-butyne-2-alcohol molar weight 0.02～0.5%; Described metal halide is cuprous chloride, cuprous bromide or cuprous iodide, its consumption be 2-methyl-3-butyne-2-alcohol molar weight 0. 5～1.2%;(2) 2,2-dimethyl tetrahydro pyrans-4-one synthetic: taking mercury salt and sulfuric acid as composite catalyst, make 2-methyl-5-hexene-3-alkynes-2-alcohol and water in 80～110 DEG C of addition reactions 10～15 hours; After reacting completely, be cooled to room temperature, adjust pH=7～9; Extraction, anhydrous sodium sulfate drying, filtration, precipitation, underpressure distillation, obtains product 2,2-dimethyl tetrahydro pyrans-4-one;Described mercury salt is mercuric acetate or Mercury bisulfate, the amount of mercury salt be 2-methyl-5-hexene-3-alkynes-2-alcohol molar weight 1～6%; The amount of described sulfuric acid be 2-methyl-5-hexene-3-alkynes-2-alcohol molar weight 14～73%;(3) 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester synthetic: taking toluene as solvent, under alkali effect, 2,2-dimethyl tetrahydro pyrans-4-one and ethyl chloroacetate are with the mixed in molar ratio of 1:1～1:1.5, room temperature reaction 4～7 hours, add water and separate organic phase, organic phase washing, anhydrous sodium sulfate drying, precipitation, obtain 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester;(4) 2,2-dimethyl tetrahydro pyrans-4-formaldehyde is synthetic: by 5,5-dimethyl-1,6-dioxo spiro [2.5] octane-2-carboxylic acid, ethyl ester and inorganic alkali solution are with the mixed in molar ratio of 1:1～1:1.5, stirring at room temperature reaction 10～15 hours, then be warming up to 95～105 DEG C, add 1～3M hydrochloric acid to carry out acidolysis, collect the product of generation and the mixture of water, extraction, precipitation, obtains product 2,2-dimethyl tetrahydro pyrans-4-formaldehyde;Synthesizing of (5) 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acids: by soluble in water 2,2-dimethyl tetrahydro pyrans-4-formaldehyde, add oxygenant, stirring reaction 10～15 hours, filters, and filtrate adjusts pH to separating out solid, filter, obtain target product 2,2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid.
- 2. as claimed in claim 12, the synthetic method of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, it is characterized in that: the described alkali of step (1) is triethylamine, at least one in diethylamine, pyridine, the consumption of alkali is 1～5 times of molar weight of 2-methyl-3-butyne-2-alcohol.
- 3. as claimed in claim 12, the synthetic method of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, is characterized in that: the described alkali of step (3) is sodium amide, sodium ethylate, sodium methylate; The consumption of alkali is 1～1.6 times of synthetic molar weight of 2-methyl-5-hexene-3-alkynes-2-alcohol.
- 4. as claimed in claim 12, the synthetic method of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, is characterized in that: inorganic alkali solution described in step (4) is sodium hydroxide solution or the potassium hydroxide solution of mass concentration 10%～35%.
- 5. as claimed in claim 12, the synthetic method of 2-dimethyl tetrahydro-2H-pyrans-4-carboxylic acid, is characterized in that: in step (5), oxygenant is potassium permanganate, oxygen or hydrogen peroxide, the consumption of oxygenant is 1～6 times of 2,2-dimethyl tetrahydro pyrans-4-formaldehyde molar weight.
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