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Synthetic method of pholcodine

A synthetic method and pholkidine technology, applied in organic chemistry methods, organic chemistry and other directions, can solve the problems of large required amount, many reaction steps, reduced difficulty and safety risk, etc., and achieve easy quality and simple reaction steps. Effect

Active Publication Date: 2019-02-15
YICHANG HUMANWELL PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] This method uses more highly toxic and highly corrosive reagents, and the repeated use of strong acid and strong alkali reagents in large quantities. Most of the organic solvents used are flammable and explosive solvents and the required amount is relatively large. The condensation reaction process requires higher conditions. , it is easy to generate elimination products, and the overall reaction steps are more difficult for the generation operation and bring safety risks, which reduces the yield of the final product

Method used

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  • Synthetic method of pholcodine
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  • Synthetic method of pholcodine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] 1) 285.3g morphine base is dissolved in the DMF solution of 2000ml.

[0049] 2) Dissolve 282g of 1,2-dibromoethane in 800ml of DMF solution and add 110g of anhydrous sodium carbonate. Under nitrogen protection, the temperature was raised to 60° C., and the DMF solution of morphine base prepared in 1) was slowly dropped into the 1,2-dibromoethane solution under stirring. After the dropwise addition was completed, the insulation reaction was continued for 2 hours.

[0050] 3) After the reaction is complete, distill under reduced pressure until there is no liquid drop, add 550ml of purified water and stir to dissolve the inorganic salt. The insoluble matter was collected by filtration and dried.

[0051] 4) 105g morpholine and 3) insolubles are dissolved in 2000ml DMF, and add 110g anhydrous sodium carbonate and 10g nano CuI powder. Under the protection of nitrogen, the temperature was raised to 115° C. for 6 hours.

[0052] 5) Suction filtration while hot, collect the...

Embodiment 2

[0064] 1) 285.3g morphine base is dissolved in the DMF solution of 2000ml.

[0065] 2) Dissolve 423g of 1,2-diiodoethane in 800ml of DMF solution and add 110g of anhydrous sodium carbonate. Under nitrogen protection, the temperature was raised to 60° C., and the DMF solution of morphine base prepared in 1) was slowly dropped into the 1,2-diiodoethane solution under stirring. After the dropwise addition was completed, the insulation reaction was continued for 2 hours.

[0066] 3) After the reaction is complete, distill under reduced pressure until there is no liquid drop, add 550ml of purified water and stir to dissolve the inorganic salt. The insoluble matter was collected by filtration and dried.

[0067] 4) 105g morpholine and 3) insolubles are dissolved in 2000ml DMF, and add 110g anhydrous sodium carbonate and 10g nano CuI powder. Under the protection of nitrogen, the temperature was raised to 115° C. for 8 hours.

[0068] 5) Suction filtration while it is hot, collect...

Embodiment 3

[0078] 1) Dissolve 285.3g of morphine base in 2000ml of DMSO solution.

[0079] 2) Dissolve 282g of 1,2-dibromoethane in 800ml of DMSO solution and add 140g of anhydrous potassium carbonate. Under nitrogen protection, the temperature was raised to 60° C., and the DMF solution of morphine base prepared in 1) was slowly dropped into the 1,2-dibromoethane solution under stirring. After the dropwise addition was completed, the insulation reaction was continued for 2 hours.

[0080] 3) After the reaction is complete, distill under reduced pressure until there is no liquid drop, add 550ml of purified water and stir to dissolve the inorganic salt. The insoluble matter was collected by filtration and dried.

[0081] 4) 105g morpholine and 3) insolubles are dissolved in 2000ml DMSO, and 140g anhydrous potassium carbonate and 10g nano CuI powder are added. Under the protection of nitrogen, the temperature was raised to 120° C. for 7 hours.

[0082] 5) Suction filtration while hot, c...

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Abstract

The invention discloses a synthetic method of pholcodine. The synthetic method of pholcodine comprises the steps of deriving a phenolic hydroxyl group of a morphine base as a starting material to prolong the branch, then reacting the intermediate with an amine group on morpholine to generate crude pholcodine, and refining the crude pholcodine by means of purification to obtain pholcodine. The method is simple in reaction steps and economical and readily available in reagents, avoids the risk of using a large amount of highly toxic, flammable and explosive solvents, and greatly improves the yield and purity of the product.

Description

technical field [0001] The invention relates to the field of compound drug synthesis, in particular to a synthesis method of pholcodine. Background technique [0002] Pholcodine, also known as morphine or pholcodine, is a semi-synthetic derivative of morphine. It is a central antitussive suppressant with sedative and analgesic effects, similar to codeine, but its oral antitussive effect is stronger than codeine, its addiction is weaker, and its respiratory depression effect is smaller than that of morphine. For the treatment of severe dry cough and moderate pain, newborns and children are easy to tolerate this drug, and will not cause constipation and digestive disorders. The structural formula is as follows: [0003] [0004] There are not many synthetic methods reported for pholcodine, and the reported synthetic methods are usually to synthesize morpholine into morpholine ethanol, then chlorinate it into ethyl morpholine hydrochloride, and finally form it by condensat...

Claims

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Application Information

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IPC IPC(8): C07D489/02
CPCC07B2200/07C07D489/02
Inventor 赵伟刘杨王孟华曾华荣张建勋周雪平熊秀琳于飞赵晓柯
Owner YICHANG HUMANWELL PHARMA
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