CN102977063A - Method for synthesizing 2-morpholine-8-phenyl-4-benzopyran-4-one - Google Patents
Method for synthesizing 2-morpholine-8-phenyl-4-benzopyran-4-one Download PDFInfo
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- CN102977063A CN102977063A CN2012104840216A CN201210484021A CN102977063A CN 102977063 A CN102977063 A CN 102977063A CN 2012104840216 A CN2012104840216 A CN 2012104840216A CN 201210484021 A CN201210484021 A CN 201210484021A CN 102977063 A CN102977063 A CN 102977063A
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Abstract
The invention discloses a method for synthesizing 2-morpholine-8-phenyl-4-benzopyran-4-one. Under the premise of taking 2-hydroxyl-3 carboxylic acid biphenyl as a raw material, two methods are tried, and finally, a technological method is determined. A first try method is that 2-hydroxyl-3 carboxylic acid biphenyl and methanol are esterified and then are condensed with acetyl morpholine, but the expected product is not obtained. A second try method is that 2-hydroxyl-3 carboxylic acid biphenyl is taken as the raw material, is esterified with methanol, is reacted with lithium diisopropylamine, is linked with 4-acetyl morpholine and is cyclized through adopting trifluoromethanesulfonic acid, so that the target product of 2-morpholine-8-phenyl-4-benzopyran-4-one is obtained. After the technology is adopted, 2-morpholine-8-phenyl-4-benzopyran-4-one is produced, and the yield of 2-morpholine-8-phenyl-4-benzopyran-4-one is increased.
Description
Technical field
The synthesis technology that the present invention relates to a kind of 2-morpholine-8-phenyl-4-benzopyran-4-one improves, and belongs to medicine, chemical technology field.
Background technology
2-morpholine-8-phenyl-4-benzopyran-4-one is a kind of white solid, is important medicine intermediate, raw material.
Now find the synthesis technique with 2-morpholine-8-phenyl-4-benzopyran-4-one; to adopt take 2 – hydroxyl-3 carboxylic acid biphenyls as raw material; with after methyl alcohol becomes ester again with the diisopropylamine lithium effect after; after connecting with 4-ethanoyl morpholine, obtain target product 2-morpholine-8-phenyl-4-benzopyran-4-one after closing ring with trifluoromethanesulfanhydride anhydride.Synthesizing of the 2-morpholine that realizes-8-phenyl-4-benzopyran-4-one, and the path is short, and cost is low.
Summary of the invention
For domestic without bibliographical information, the present invention take 2 – hydroxyl-3 carboxylic acid biphenyls under the prerequisite of raw material, attempted two circuits after, finally determined the technique circuit of this patent.Article one, attempting circuit is, 2 – hydroxyl-3 carboxylic acid biphenyls with after methyl alcohol becomes ester again with the condensation of ethanoyl morpholine, still fail the product that obtains wanting.Second is attempted circuit; be raw material in order to 2 – hydroxyl-3 carboxylic acid biphenyls; with after methyl alcohol becomes ester again with the diisopropylamine lithium effect after, after connecting with 4-ethanoyl morpholine, obtain target product 2-morpholine-8-phenyl-4-benzopyran-4-one after closing ring with trifluoromethanesulfanhydride anhydride.Adopt this technique, realized 2-morpholine-8-phenyl-4-benzopyran-4-one, improved the yield of 2-morpholine-8-phenyl-4-benzopyran-4-one.
The synthetic method of 2-morpholine of the present invention-8-phenyl-4-benzopyran-4-one; that route reacts after adopting improvement; take 2 – hydroxyl-3 carboxylic acid biphenyls as raw material; with after methyl alcohol becomes ester again with the diisopropylamine lithium effect after; after connecting with 4-ethanoyl morpholine, obtain target product 2-morpholine-8-phenyl-4-benzopyran-4-one after closing ring with trifluoromethanesulfanhydride anhydride.
The synthetic method of above-mentioned 2-morpholine-8-phenyl-4-benzopyran-4-one; it is characterized in that: described improvement is take 2 – hydroxyl-3 carboxylic acid biphenyls as raw material; with after methyl alcohol becomes ester again with the diisopropylamine lithium effect after; after connecting with 4-ethanoyl morpholine, close with trifluoromethanesulfanhydride anhydride and to obtain route after target product 2-morpholine-8-phenyl-this improvement of 4-benzopyran-4-one behind the ring.
The synthetic method of above-mentioned 2-morpholine-8-phenyl-4-benzopyran-4-one is characterized in that: described employing diisopropylamine lithium carries out the condensation of second step as alkali.
The synthetic method of above-mentioned 2-morpholine-8-phenyl-4-benzopyran-4-one, it is characterized in that: the synthetic method of described 2-morpholine-8-phenyl-4-benzopyran-4-one makes: add 2 – hydroxyl-3 carboxylic acid biphenyls (15.3 gram) in the there-necked flask of 500 ml, methyl alcohol (230ml) drips the vitriol oil (20.35 gram), be heated to 80 ℃, thin layer chromatography board tracks to reaction and finishes, spin off most of methyl alcohol, add water 60ml, dichloromethane extraction, the saturated sodium bicarbonate washing, the dry post of crossing gets 2 – hydroxyl-3 carboxylate methyl ester biphenyl (15 gram).In the there-necked flask of the 500ml of set diisopropylamine lithium, add 4-ethanoyl morpholine (11 gram); 0 ℃ of lower stirring 1 hour; then the tetrahydrofuran solution that adds 2 – hydroxyl-3 carboxylate methyl ester biphenyl (12.14 gram); at room temperature spend the night again; inferior daily 10% hydrochloric acid cancellation, dichloromethane extraction.Be spin-dried for post and got 1-(2-hydroxyl-biphenyl)-3-(1,3-propanedione) morpholine (21.64 gram).In 500ml single port bottle, add 1-(2-hydroxyl-biphenyl)-3-(1, the 3-propanedione) morpholine (21.64 gram), methylene dichloride (250ml) drips trifluoromethanesulfanhydride anhydride (46.92 gram), at room temperature spends the night.Be spin-dried for next day, and remainder stirred 4 hours with methanol solution, is spin-dried for, with in the half saturated sodium bicarbonate and dichloromethane extraction again.The dry post of crossing gets target product 2-morpholine-8-phenyl-4-benzopyran-4-one (11 gram).
Above-mentioned with 2 – hydroxyl-3 carboxylic acid biphenyls, methyl alcohol, diisopropylamine lithium and trifluoromethanesulfanhydride anhydride etc. are as follows for chemical reaction and the reaction formula of the synthetic 2-morpholine of raw material-8-phenyl-4-benzopyran-4-one:
The reaction equation of (1) 2 – hydroxyl-3 carboxylic acid biphenyl and methyl alcohol is:
(2) reaction is finished, and after the thick purifying and after the diisopropylamine lithium effect with the reaction equation of 4-ethanoyl morpholine is again:
(3) reaction is finished, and closes the change reaction equation of encircling by trifluoromethanesulfanhydride anhydride behind the purifying to be:
Embodiment
Embodiment:
The synthetic method of described 2-morpholine-8-phenyl-4-benzopyran-4-one makes: add 2 – hydroxyl-3 carboxylic acid biphenyls (15.3 gram) in the there-necked flask of 500 ml, methyl alcohol (230ml) drips the vitriol oil (20.35 gram), be heated to 80 ℃, thin layer chromatography board tracks to reaction and finishes, spin off most of methyl alcohol, add water 60ml, dichloromethane extraction, the saturated sodium bicarbonate washing, the dry post of crossing gets 2 – hydroxyl-3 carboxylate methyl ester biphenyl (15 gram).In the there-necked flask of the 500ml of set diisopropylamine lithium, add 4-ethanoyl morpholine (11 gram); 0 ℃ of lower stirring 1 hour; then the tetrahydrofuran solution that adds 2 – hydroxyl-3 carboxylate methyl ester biphenyl (12.14 gram); at room temperature spend the night again; inferior daily 10% hydrochloric acid cancellation, dichloromethane extraction.Be spin-dried for post and got 1-(2-hydroxyl-biphenyl)-3-(1,3-propanedione) morpholine (21.64 gram).In 500ml single port bottle, add 1-(2-hydroxyl-biphenyl)-3-(1, the 3-propanedione) morpholine (21.64 gram), methylene dichloride (250ml) drips trifluoromethanesulfanhydride anhydride (46.92 gram), at room temperature spends the night.Be spin-dried for next day, and remainder stirred 4 hours with methanol solution, is spin-dried for, with in the half saturated sodium bicarbonate and dichloromethane extraction again.The dry post of crossing gets target product 2-morpholine-8-phenyl-4-benzopyran-4-one (11 gram).
Claims (4)
1.2-the synthetic method of morpholine-8-phenyl-4-benzopyran-4-one; that route reacts after adopting improvement; take 2 – hydroxyl-3 carboxylic acid biphenyls as raw material; with after methyl alcohol becomes ester again with the diisopropylamine lithium effect after; after connecting with 4-ethanoyl morpholine, obtain target product 2-morpholine-8-phenyl-4-benzopyran-4-one after closing ring with trifluoromethanesulfanhydride anhydride.
2. the synthetic method of 2-morpholine-8-phenyl-4-benzopyran-4-one as claimed in claim; it is characterized in that: described improvement is take 2 – hydroxyl-3 carboxylic acid biphenyls as raw material; with after methyl alcohol becomes ester again with the diisopropylamine lithium effect after; after connecting with 4-ethanoyl morpholine, close with trifluoromethanesulfanhydride anhydride and to obtain route after target product 2-morpholine-8-phenyl-this improvement of 4-benzopyran-4-one behind the ring.
3. the synthetic method of 2-morpholine-8-phenyl-4-benzopyran-4-one as claimed in claim, it is characterized in that: described employing diisopropylamine lithium carries out the condensation of second step as alkali.
4. the synthetic method of 2-morpholine-8-phenyl-4-benzopyran-4-one as claimed in claim; it is characterized in that: the synthetic method of described 2-morpholine-8-phenyl-4-benzopyran-4-one makes: add 2 – hydroxyl-3 carboxylic acid biphenyls (15.3 gram) in the there-necked flask of 500 ml; methyl alcohol (230ml) drips the vitriol oil (20.35 gram); be heated to 80 ℃; thin layer chromatography board tracks to reaction and finishes; spin off most of methyl alcohol; add water 60ml; dichloromethane extraction; the saturated sodium bicarbonate washing; the dry post of crossing gets 2 – hydroxyl-3 carboxylate methyl ester biphenyl (15 gram); in the there-necked flask of the 500ml of set diisopropylamine lithium, add 4-ethanoyl morpholine (11 gram); 0 ℃ of lower stirring 1 hour; then the tetrahydrofuran solution that adds 2 – hydroxyl-3 carboxylate methyl ester biphenyl (12.14 gram); at room temperature spend the night again; inferior daily 10% hydrochloric acid cancellation; dichloromethane extraction; be spin-dried for post and got 1-(2-hydroxyl-biphenyl)-3-(1; the 3-propanedione) morpholine (21.64 gram); in 500ml single port bottle, add 1-(2-hydroxyl-biphenyl)-3-(1; the 3-propanedione) morpholine (21.64 gram); methylene dichloride (250ml); drip trifluoromethanesulfanhydride anhydride (46.92 gram); at room temperature spend the night; be spin-dried for next day; remainder stirred 4 hours with methanol solution; be spin-dried for, with in the half saturated sodium bicarbonate and dichloromethane extraction, the dry post of crossing gets target product 2-morpholine-8-phenyl-4-benzopyran-4-one (11 gram) again.
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| CN2012104840216A CN102977063A (en) | 2012-11-26 | 2012-11-26 | Method for synthesizing 2-morpholine-8-phenyl-4-benzopyran-4-one |
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| CN2012104840216A CN102977063A (en) | 2012-11-26 | 2012-11-26 | Method for synthesizing 2-morpholine-8-phenyl-4-benzopyran-4-one |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003024949A1 (en) * | 2001-08-14 | 2003-03-27 | Cancer Research Technology Limited | Dna-pk inhibitors |
| WO2009094560A2 (en) * | 2008-01-24 | 2009-07-30 | Semafore Pharmaceuticals, Inc. | Thienopyranones as kinase inhibitors |
| CN101965408A (en) * | 2008-02-04 | 2011-02-02 | 塞尔卓姆股份公司 | Selectivity profiling of pi3k interacting molecules against multiple targets |
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- 2012-11-26 CN CN2012104840216A patent/CN102977063A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003024949A1 (en) * | 2001-08-14 | 2003-03-27 | Cancer Research Technology Limited | Dna-pk inhibitors |
| WO2009094560A2 (en) * | 2008-01-24 | 2009-07-30 | Semafore Pharmaceuticals, Inc. | Thienopyranones as kinase inhibitors |
| CN101965408A (en) * | 2008-02-04 | 2011-02-02 | 塞尔卓姆股份公司 | Selectivity profiling of pi3k interacting molecules against multiple targets |
Non-Patent Citations (1)
| Title |
|---|
| COLTART DON M. ET AL: "Direct Carbon一Carbon Bond Formation via Chemoselective Soft Enolization of Thioesters:A Remarkably Simple and Versatile Crossed-Claisen Reaction Applied to the Synthesis of LY294002", 《ORGANIC LETTERS》 * |
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