CN114315851A - Method for synthesizing glabridin drug intermediate - Google Patents
Method for synthesizing glabridin drug intermediate Download PDFInfo
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- CN114315851A CN114315851A CN202210000186.5A CN202210000186A CN114315851A CN 114315851 A CN114315851 A CN 114315851A CN 202210000186 A CN202210000186 A CN 202210000186A CN 114315851 A CN114315851 A CN 114315851A
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- LBQIJVLKGVZRIW-ZDUSSCGKSA-N glabridin Chemical compound C1([C@H]2CC3=CC=C4OC(C=CC4=C3OC2)(C)C)=CC=C(O)C=C1O LBQIJVLKGVZRIW-ZDUSSCGKSA-N 0.000 title claims abstract description 31
- 229940093767 glabridin Drugs 0.000 title claims abstract description 31
- PMPYOYXFIHXBJI-ZDUSSCGKSA-N glabridin Natural products C1([C@H]2CC=3C=CC4=C(C=3OC2)CCC(O4)(C)C)=CC=C(O)C=C1O PMPYOYXFIHXBJI-ZDUSSCGKSA-N 0.000 title claims abstract description 31
- LBQIJVLKGVZRIW-UHFFFAOYSA-N glabridine Natural products C1OC2=C3C=CC(C)(C)OC3=CC=C2CC1C1=CC=C(O)C=C1O LBQIJVLKGVZRIW-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 229940079593 drug Drugs 0.000 title claims abstract description 17
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 239000003054 catalyst Substances 0.000 claims abstract description 17
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 12
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims abstract description 10
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- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
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- 235000008696 isoflavones Nutrition 0.000 claims abstract description 6
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- 238000006462 rearrangement reaction Methods 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000007787 solid Substances 0.000 claims description 17
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 15
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 11
- 238000010438 heat treatment Methods 0.000 claims description 11
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 claims description 10
- 238000010992 reflux Methods 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 238000012544 monitoring process Methods 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- XVOCYIHGQROGNT-UHFFFAOYSA-N 1,1-dimethoxy-3-methylbut-2-ene Chemical compound COC(OC)C=C(C)C XVOCYIHGQROGNT-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 239000012535 impurity Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 9
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 3
- 229930003935 flavonoid Natural products 0.000 description 3
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- 150000002215 flavonoids Chemical class 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
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- 108090001060 Lipase Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000011161 development Methods 0.000 description 2
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- 235000019421 lipase Nutrition 0.000 description 2
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- NIUZVSQOXJIHBL-UHFFFAOYSA-N 1-bromo-2,4-dimethoxybenzene Chemical compound COC1=CC=C(Br)C(OC)=C1 NIUZVSQOXJIHBL-UHFFFAOYSA-N 0.000 description 1
- VQTDPCRSXHFMOL-UHFFFAOYSA-N 2,4-Dimethoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C(OC)=C1 VQTDPCRSXHFMOL-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
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- 241000202807 Glycyrrhiza Species 0.000 description 1
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- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
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- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a method for synthesizing a glabridin drug intermediate, belonging to the field of organic synthesis. 1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone is used as a raw material, and the glabridin drug intermediate, namely the isoflavone with the dihydropyran ring, is obtained through aldol condensation reaction and rearrangement reaction. The synthesis method disclosed by the invention has the advantages that the reaction conditions are easy to control, the operation is simpler, the method is suitable for large-batch production, no hydrogen addition is needed, no noble metal catalyst is used, the cost is low, the total yield is higher and reaches more than 60% from the compound I to the compound IV through three-step reaction, and the method has a good application prospect.
Description
Technical Field
The invention relates to a method for synthesizing a glabridin drug intermediate, belonging to the field of organic synthesis.
Background
Glabradine (Glabradin) is a flavonoid substance, also called Glabridin, is the most main isoflavone component in Glycyrrhiza glabra, accounts for about 11 percent of total flavonoid components of Glycyrrhiza glabra, has the effects of whitening, resisting bacteria, resisting allergy, resisting cancer, resisting oxidation, eliminating free radicals, reducing blood fat, reducing blood pressure and the like, is highly valued in the research of aspects of beauty, cosmetics, medicines, health care and the like, and has good development prospect. At present, the obtaining way of glabridin in China is mainly to extract from a precious plant of glabrous licorice, and a large amount of glabridin cannot be obtained, and the extraction process is mostly to extract total flavonoids by using an organic solvent, separate by using column chromatography, and repeatedly recrystallize to obtain the glabridin, so that the method is complex, and the development of an effective chemical synthesis method for preparing the glabridin becomes more important.
2013, Wenhua in the patent of a glabridin synthesis method (CN 103030647A) discloses a more complete synthesis path, 2, 4-dimethoxyacetophenone is used as a raw material to prepare the glabridin, the synthesis path is shown as follows, the total yield is about 20%, but the addition reaction in the step 4 needs hydrogen and noble metal palladium as a catalyst, the experimental method is dangerous and high in cost, and the catalyst is difficult to completely remove, so that the difficulty is brought to the subsequent purification of the glabridin.
In 2018, the patent "a synthetic method of glabridin" (CN 109232603a) discloses a method for preparing racemic glabridin by 7-step reaction with 7-hydroxycoumarin as an initial raw material, wherein the total yield is only 20%, the key step is Suzuki coupling reaction, and a required boric acid reagent and a metal palladium catalyst are expensive and have high cost; 2021 patent "a method for synthesizing optically pure glabridin" (CN 113651832a) discloses a method for obtaining glabridin by 9 steps of reaction using 2, 4-dimethoxybromobenzene as raw material, but the key reaction steps need fungal lipase or bacterial lipase, and the steps are complicated and professional, and are not suitable for large-scale production.
Aiming at the defects of the prior art, the invention improves the synthesis method of glabridin (CN 103030647A), provides a synthesis method of a glabridin drug intermediate, takes 1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone as a raw material, obtains the glabridin drug intermediate, namely isoflavone with a dihydropyran ring through aldol condensation reaction and rearrangement reaction, and can obtain the glabridin only by simple steps in the following process. The synthesis method has the advantages of easily controlled reaction conditions, simpler operation, suitability for mass production in proportion, no need of hydrogen addition and noble metal catalyst, low cost, higher total yield and good application prospect.
Disclosure of Invention
The invention provides a method for synthesizing a glabridin drug intermediate. 1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone is used as a raw material, and a glabridin drug intermediate, namely isoflavone with a dihydropyran ring, is obtained through aldol condensation reaction and rearrangement reaction, and the glabridin can be obtained only through simpler steps in the following steps, wherein the reaction route is shown as follows:
step 1: dissolving 1-10 g of 1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone in 10-100 mL of toluene, dropwise adding 0.62-6.20 mL of 1, 1-dimethoxy-3-methyl-2-butene and 0.42-4.20 mL of 3-methylpyridine, refluxing, heating, reacting, monitoring the reaction process by thin-layer chromatography (TLC), after the reaction is completed, washing with diluted hydrochloric acid to remove the 3-methylpyridine, washing with water and saturated salt solution to remove water-soluble impurities, drying with anhydrous sodium sulfate, carrying out suction filtration, and spin-drying to obtain a yellow solid compound II;
step 2: dissolving 1-10 g of a compound II in 28-280 mL of ethanol, adding 0.33-3.3 mL of 37% formaldehyde aqueous solution and 0.4-4.0 mL of an alkali catalyst, refluxing, heating and reacting, monitoring the reaction process by TCL, performing spin drying after the reaction is completed to obtain a yellow oily substance, and separating and purifying to obtain a yellow solid compound III;
and step 3: heating and dissolving 1-10 g of the compound III by using 28-280 mL of ethanol, dropwise adding 0.3-3.0 mL of an alkali catalyst, carrying out reflux heating reaction, monitoring the reaction process by using TCL (thermal conductive liquid chromatography), cooling to room temperature after the reaction is completed, separating out a solid, and washing by using 0 ℃ ethanol to obtain a white solid compound IV, namely the glabridin drug intermediate.
Description of the drawings:
FIG. 1 is a reaction scheme
FIG. 2 is a hydrogen spectrum of compound II;
FIG. 3 is a carbon spectrum of compound II;
FIG. 4 shows a hydrogen spectrum of compound III;
FIG. 5 is a carbon spectrum of compound III;
FIG. 6 shows a hydrogen spectrum of Compound IV;
FIG. 7 shows a carbon spectrum of Compound IV.
The specific implementation mode is as follows:
the invention is illustrated in detail below with reference to the examples:
the synthesis method of isoflavone with dihydropyran ring in the embodiment comprises the following steps:
example 1:
(1) synthesis of Compound II
Dissolving 5.76 g (0.02 mol) of 1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone in 50 mL of toluene, adding 3.6 mL (0.024 mol) of 1, 1-dimethoxy-3-methyl-2-butene and 2.4 mL (0.024 mol) of 3-methylpyridine, refluxing, heating, reacting, monitoring the reaction process by TCL, washing with dilute hydrochloric acid to remove 3-methylpyridine after the reaction is completed, washing with water and saturated saline to remove water-soluble impurities, drying with anhydrous sodium sulfate, filtering, and spin-drying to obtain a yellow solid compound II with the mass of 5.56 g and the yield of 79%. The hydrogen spectrum is shown in figure 2 of the drawings,1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 7.84 to 7.86 (d, 1H, J =8.45Hz), 7.01 to 7.04 (d, 1H, J =8.23Hz), 6.54 to 6.56 (d, 1H, J =10.06Hz), 6.51 (s, 1H), 6.43 to 6.45 (d, 1H, J =8.46Hz), 6.35 to 6.38 (d, 1H, J =8.69Hz), 5.70 to 5.72 (d, 1H, J =10.01Hz), 4.13 (s, 2H), 3.70 (s, 3H), 3.67 (s, 3H), 1.37 (s, 6H). The carbon spectrum is shown in figure 3 of the drawings,13C NMR (400 MHz, DMSO-d6) δ 203.86, 160.30, 159.37, 159.10, 158.47, 132.60, 131.97, 129.56, 115.83, 115.42, 113.51, 108.96, 108.62, 105.18, 98.92, 78.16, 55.99, 55.70, 38.84, 28.37。
synthesis of Compound III
3.54 g (0.01 mol) of the compound II is dissolved in 100mL of ethanol, 1.19 mL (0.012 mol) of 37 percent formaldehyde aqueous solution and 1.5 mL (0.012 mol) of diethylamine are added dropwise, the mixture is heated under reflux, the reaction process is monitored by TCL, after the reaction is completed, yellow oily matter is obtained by rotary drying, and yellow solid compound III with the mass of 2.97 g and the yield of 81 percent is obtained by silica gel column chromatography. The hydrogen spectrum is shown in figure 4 of the drawings,1H NMR (400 MHz, CDCl3) δ 12.80 (s, 1H), 7.50 to 7.52 (d, 1H, J =8.82Hz), 7.30 to 7.32 (d, 1H, J =8.42Hz), 6.72 to 6.75 (d, 1H, J =10.04Hz), 6.51 to 6.54 (d, 1H, J =11.26Hz), 6.38 (s, 1H), 6.19 to 6.22 (d, 1H, J =9.22Hz), 5.83 (s, 1H), 5.55 to 5.58 (d, 1H, J =10.15Hz), 5.50 (s, 1H), 3.80 (s, 3H), 3.56 (s, 3H), 1.44 (s, 6H). The carbon spectrum is shown in figure 5 of the drawings,13C NMR (400 MHz, CDCl3) δ 201.65, 161.67, 160.10, 159.46, 157.51, 145.18, 133.83, 130.12, 128.06, 120.99, 120.60, 115.99, 113.20, 109.15, 107.76, 105.48, 99.05, 77.70, 55.60, 55.53, 28.47。
(3) synthesis of Compound IV
1.83 g (0.005 mol) of the compound III is heated and dissolved in 50 mL of ethanol, then 0.55 mL (0.006 mol) of morpholine is added, the reaction process is monitored by TCL, after the reaction is completed, the mixture is cooled to room temperature, a solid is separated out, and the solid is washed by ethanol at 0 ℃ to obtain a white solid compound IV, namely the glabridin drug intermediate, the mass of the white solid compound IV is 1.80 g, and the yield of the white solid compound IV is 98%. The hydrogen spectrum is shown in figure 6 of the drawings,1h NMR (400 MHz, DMSO-d6) δ 7.58 (d, 1H, J =8.6 Hz), 6.97 (d, 1H, J = 8.3 Hz), 6.57-6.42 (m, 4H), 5.74 (d, 1H, J =10.0 Hz), 4.55 (d, 1H, J = 11.5 Hz), 4.47 (dd, 1H, J = 10.9, 5.5 Hz), 4.17 (dd, 1H, J = 11.5, 5.4 Hz), 3.71 (s, 3H), 3.68 (s, 3H), 1.38 (d, 6H, J =8.8 Hz). The carbon spectrum is shown in figure 7 of the drawings,13C NMR (400 MHz, DMSO-d6) δ 191.07, 160.62, 158.88, 158.73, 157.87, 131.35, 130.23, 128.35, 116.31, 115.60, 115.49, 111.03, 109.32, 105.51, 99.40, 77.98, 71.13, 56.18, 55.76, 47.24, 28.46, 28.24。
example 2:
preparation of compound ii: dissolving 5.76 g (0.02 mol) of 1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone in 50 mL of toluene, adding 3.6 mL (0.024 mol) of 1, 1-dimethoxy-3-methyl-2-butene and 2.4 mL (0.024 mol) of pyridine, refluxing, heating, reacting, monitoring the reaction process by TCL (trichloroacetic acid), washing with dilute hydrochloric acid to remove pyridine after the reaction is completed, washing with water and saturated saline to remove water-soluble impurities, drying with anhydrous sodium sulfate, filtering, and spin-drying to obtain a yellow solid compound II with the mass of 5.02 g and the yield of 71%.
Compounds III and IV were synthesized as in example 1.
Example 3:
the synthesis of compound ii was performed as in example 1;
preparation of compound iii: 3.54 g (0.01 mol) of the compound II is dissolved in 100mL of ethanol, 1.19 mL (0.012 mol) of 37 percent formaldehyde aqueous solution and 1.5 mL of ethylenediamine are added dropwise, the reflux heating reaction is carried out, the reaction progress is monitored by TCL, after the reaction is completed, yellow oily matter is obtained by spin drying, and yellow solid compound III is obtained by silica gel column chromatography, the mass is 2.85 g, and the yield is 78 percent.
The synthesis of compound IV is the same as in example 1.
Claims (5)
1. A synthetic method of a glabridin drug intermediate is characterized by comprising the following steps:
1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone is used as a raw material, and the glabridin drug intermediate, namely isoflavone with a dihydropyran ring, is obtained through aldol condensation reaction and rearrangement reaction;
the reaction route is as follows:
2. the method of synthesis according to claim 1, characterized by the steps of:
step 1: dissolving 1-10 g of 1- (2, 4-dihydroxyphenyl) -2- (3, 4-dimethoxy) ethanone in 10-100 mL of toluene, dropwise adding 0.62-6.20 mL of 1, 1-dimethoxy-3-methyl-2-butene and 0.42-4.20 mL of alkali catalyst, carrying out reflux heating reaction, monitoring the reaction process by TLC (thin layer chromatography), washing with dilute hydrochloric acid to remove the alkali catalyst after the reaction is completed, washing with water and saturated salt solution to remove water-soluble impurities, drying with anhydrous sodium sulfate, carrying out suction filtration, and carrying out spin drying to obtain a yellow solid compound II;
step 2: dissolving 1-10 g of a compound II in 28-280 mL of ethanol, adding 0.33-3.3 mL of 37% formaldehyde aqueous solution and 0.4-4.0 mL of an alkali catalyst, refluxing, heating and reacting, monitoring the reaction process by TCL, performing spin drying after the reaction is completed to obtain a yellow oily substance, and separating and purifying to obtain a yellow solid compound III;
and step 3: heating and dissolving 1-10 g of the compound III by using 28-280 mL of ethanol, dropwise adding 0.3-3.0 mL of an alkali catalyst, carrying out reflux heating reaction, monitoring the reaction process by using TCL (thermal conductive liquid chromatography), cooling to room temperature after the reaction is completed, separating out a solid, and washing by using 0 ℃ ethanol to obtain a white solid compound IV, namely the glabridin drug intermediate.
3. The method of synthesis according to claim 2, characterized in that:
the alkali catalyst used in the step 1 is 3-methylpyridine or pyridine, and the molar ratio of the compound I, 1-dimethoxy-3-methyl-2-butene and the alkali catalyst is 1: 1.2-1.5.
4. The method for synthesizing glabridin drug intermediate according to claim 2, wherein:
the alkali catalyst used in the step 2 is diethylamine, morpholine or ethylenediamine, and the molar ratio of the compound II, the 37% formaldehyde aqueous solution and the alkali catalyst is 1: 1.2-1.5.
5. The method for synthesizing glabridin drug intermediate according to claim 2, wherein:
the alkali catalyst used in the step 3 is diethylamine, morpholine or ethylenediamine, and the molar ratio of the compound III to the alkali catalyst is 1: 1.2-1.5.
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