CN106831347A - The preparation method of 15 hydroxyl dehydroabietanes and its intermediate - Google Patents

The preparation method of 15 hydroxyl dehydroabietanes and its intermediate Download PDF

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CN106831347A
CN106831347A CN201710053945.3A CN201710053945A CN106831347A CN 106831347 A CN106831347 A CN 106831347A CN 201710053945 A CN201710053945 A CN 201710053945A CN 106831347 A CN106831347 A CN 106831347A
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converted
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tetrahydrofuran
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钱珊
王周玉
刘思言
姚昊
何彦颖
陈泉龙
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Xihua University
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    • C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
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    • C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
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Abstract

The invention discloses a kind of 15 hydroxyl dehydroabietane and its preparation method of intermediate, methods described includes for compound 1 being converted into compound 5, the step of compound 5 is converted into compound 8.The method of prepare compound of the present invention 8, by the continuous screening of process route, solves existing synthetic route in this step of hydrogen bromide addition, reaction impurities showed increased, the problem for causing product to be separated out from glacial acetic acid solution when inventory is amplified.Also, it is all higher that the inventive method often walks yield, it is easy to amplifies, it is suitable for industrialization large-scale production.

Description

The preparation method of 15- hydroxyls dehydroabietane and its intermediate
Technical field
The present invention relates to 15- hydroxyls dehydroabietane and its preparation method of intermediate.
Background technology
Rosin is a kind of important industrial chemicals, is widely used in the industries such as soap, papermaking, paint, rubber.Rosin is many The mixture of resin acid and a small amount of aliphatic acid and neutral substance is planted, wherein rosin acid is main component, with tricyclic diterpene knot Structure, rosin acid industrially has a wide range of applications.In recent years, research shows that rosin acid and its derivative have important biology Learn function.
Compound 8 is the key intermediate for preparing rosin acid derivative：
The A of CN 104370745 and the A of CN 105001049 report the syntheti c route of compound 8, but in hydrogen bromide This is walked for addition, and the reaction impurities showed increased when inventory is amplified causes product to be separated out from glacial acetic acid solution, and produces The equal very little of polarity of product, unreacting material and impurity, the purifying to product becomes very difficult, and yield is extremely low.
Therefore, it is necessary to be improved to the method for prepare compound 8.
The content of the invention
To solve the above problems, the present invention provides compound shown in a kind of prepare compound 8, or its is pharmaceutically acceptable Salt, or its solvate method, the described method comprises the following steps：
(1) compound 1 is converted into compound 5；
(2) compound 5 is converted into compound 8.
Further, the step (1) comprises the following steps：
A, by compound 1 and reaction of hydrogen bromide, prepare compound 2；
B, under alkaline environment, compound 2 is converted into compound 3；
C, compound 3 is converted into compound 4；
D, compound 4 is converted into compound 5.
Further, in the step a, solvent is acetic acid, and preferred reaction temperature is 20~30 DEG C.
Further, in the step b, alkali used is LiOH, and solvent is dimethylformamide；Preferred reaction temperature It is 80 DEG C.
Further, in the step c, including the step of compound 3 and iodoethane are reacted under alkaline environment；It is preferred that , alkali used is potassium carbonate, and solvent is acetone；Further preferred reaction temperature is 60 DEG C.
Further, in the step d, including by compound 4 and LiAlH4The step of reaction；Preferably, solvent is four Hydrogen furans；Further preferred reaction temperature is 20~30 DEG C.
Further, the step (2) comprises the following steps：
E, compound 5 is converted into compound 6；
F, compound 6 is converted into compound 7；
G, compound 7 is converted into compound 8.
Further, in the step e, including the step of compound 5 and p-methyl benzene sulfonic chloride are reacted；Preferably, Described solvent is selected from dichloromethane, pyridine, tetrahydrofuran, acetonitrile, more preferably pyridine；Further preferred reaction temperature is 20 ~30 DEG C.
Further, in the step f, including the step of compound 6 and sodium iodide and zinc powder are reacted；Preferably, institute The solvent stated is selected from DMF, dimethyl sulfoxide, HMPA, preferably HMPA；Enter one Preferred reaction temperature is walked for 105 DEG C.
Further, in the step g, including by compound 7 and SeO2The step of reaction；Preferred solvent is selected from dichloro Methane, tetrahydrofuran, acetonitrile, more preferably tetrahydrofuran；Further preferred reaction temperature is 0 DEG C.
The method of prepare compound of the invention 8, by the continuous screening of process route, solves existing synthetic route and exists This is walked for hydrogen bromide addition, and the reaction impurities showed increased when inventory is amplified causes product to be separated out from glacial acetic acid solution Problem.Also, it is all higher that the inventive method often walks yield, it is easy to amplifies, it is suitable for industrialization large-scale production.
Obviously, the above of the invention, according to the ordinary technical knowledge and customary means of this area, is not departing from Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification of other diversified forms can also be made, is replaced or is changed.
The specific embodiment of form, remakes further specifically to the above of the invention by the following examples It is bright.But this scope for being interpreted as above-mentioned theme of the invention should not be only limitted to following example.It is all based on the above of the present invention The technology realized belongs to the scope of the present invention.
Specific embodiment
In following embodiments：
Rosin acid 1 is purchased from the resistance to Jilin Chemical of peace；Lithium hydroxide, lithium aluminium hydride reduction, petroleum ether, ethyl acetate, dichloromethane, first Alcohol, acetone, pyridine, tetrahydrofuran, potassium carbonate, paratoluensulfonyl chloride, tertbutanol peroxide, glacial acetic acid, iodoethane, N, N- diformazans Base formamide, 33% hydrobromic acid etc. are purchased from Chengdu Ke Long chemical reagents factory；Zinc powder, sodium iodide, HMPA, chlorine chromium The reagents such as sour pyridinium salt, selenium dioxide are purchased from Chengdu Rui Ouke Science and Technology Ltd.s.Reagent applied in experiment is except special Illustrate outer, remaining is market is sold and analyze pure, and anhydrous reagent is processed on request with solvent；Silica gel used by thin-layer chromatography is pre- The silica GF254 prefabricated board that making sheet is produced by Qingdao Marine Chemical Co., Ltd.；Flash silica column chromatography uses Qingdao Haiyang The silica gel H of chemical plant production.
Embodiment 1
The synthetic route of compound 8 is as follows：
(a) 33%HBr/AcOH, rt., 6h, 81%；(b) LiOH, N,N-dimethylformamide, 80 DEG C, 7h, 100%； (c)EtI,K2CO3, acetone, 60 DEG C, 3h, 98%；(d)LiAlH4, tetrahydrofuran, rt., 3h, 92%；(e) TsCl, pyridine, rt, 5h, 80%；(f) Zn, NaI, HMPA, 105 DEG C, 6h, 75%；(g)SeO2, tetrahydrofuran, 0 DEG C, 5-10h, 80%.
1st, the synthesis of dibromide (2)
Compound (1) (20.00g, 66.40mmol) is dissolved in 64ml glacial acetic acid, 33%HBr/AcOH is added dropwise under ice bath Solution (64ml, 132.80mmol), is stirred at room temperature 6h, separates out a large amount of solids, and TLC display raw materials react completely.Filtering, filter cake warp Glacial acetic acid is washed to near-white, and dried in vacuum overnight obtains solid (25.00g, yield 81%), not purified direct throwing next step.
2nd, the synthesis of debrominate compound (3)
Dibromide (2) (12.00g, 25.88mmol) is dissolved in 244ml DMFs, is stirred in normal temperature Lower addition LiOH (2.64g, 64.72mmol) is mixed, 80 DEG C are warming up to, reaction solution is in water white transparency substantially, with the carrying out of reaction, Reaction solution is changed into dark brown again, reacts 7h, and TLC shows and react completely.DMF is removed in rotation, and adding water will with watery hydrochloric acid The pH of reaction solution is adjusted to 2~3, is extracted with ethyl acetate 3 times, uses saturated common salt water washing, dries, and concentration obtains faint yellow oily Thing, dried in vacuum overnight, quantitative yield.Not purified direct throwing next step.
3rd, the synthesis of compound (4)
K is added under compound (3) (15.00g, 49.67mmol) is used into 150ml acetone solutions, normal temperature2CO3(20.00g), Stirring reaction 15min.Iodoethane (11.12ml, 149.01mmol) is added dropwise in reaction solution, 60 DEG C are warming up to, with The reaction solution that carries out of reaction is changed into milk yellow.24h is reacted, TLC shows and react completely.Rotation acetone to the greatest extent, adds water, and is carried with ethyl acetate Take 3 times, use saturated common salt water washing, dry, concentration, crude product is through column chromatography (PE:EA=20：1) faint yellow solid is purified to obtain (16.15g, yield 98%).
4th, the synthesis of compound 5
Compound (4) (16.00g, 48.78mmol) 50ml tetrahydrofurans are dissolved, hydrogen is added under ice bath stirring Change in the 50ml tetrahydrofuran mixed liquors of aluminium lithium (7.00mg, 195.12mmol), there is gas to produce, reaction 3h, TLC is stirred at room temperature Display is reacted completely.PH is adjusted to 6, filtering with watery hydrochloric acid under ice bath.Rotation filtrate to the greatest extent, adds water, and is extracted 3 times with ethyl acetate, uses Saturated common salt water washing, dries, and concentration obtains water white transparency oily thing (13.45g, yield 92%).
5th, the synthesis of compound 6
The room in 100ml pyridines by compound (5) (13.00g, 45.14mmol) and TsCl (52.00g, 270.8mmol) Warm stirring reaction 5h, TLC show and react completely.Pyridine is removed in rotation, is added water, and is extracted 3 times with dichloromethane, is washed with saturated common salt Wash, dry, concentration, crude product is through column chromatography (PE:EA=60：1) water white transparency clear oil thing (15.87g, yield are purified to obtain 80%).
6th, the synthesis of compound 7
The 1ml HMPA solution of compound (6) (0.05g, 0.11mmol) is added dropwise to NaI In (0.08g, 0.54mmol) and Zn (0.07g, 1.07mmol), 105 DEG C of stirring reaction 6h are warming up to, TLC shows and react completely. Extracted 3 times with petroleum ether (the bad layering of ethyl acetate), use saturated common salt water washing, dried, concentration, crude product is through column chromatography (PE: EA=60：1) water white transparency oily thing (0.02g, yield 75%) is purified to obtain.
7th, the synthesis of compound 8
Compound (7) (0.37g, 1.36mmol) is dissolved in 265ml tetrahydrofurans, raw material is completely dissolved, added at 0 DEG C Enter SeO2The most raw material reactions of (300mg, 2.72mmol) display completely, have a small amount of big polar impurity to generate.Filtering, filtrate second Acetoacetic ester is extracted 3 times, uses saturated common salt water washing, is dried, concentration, and crude product is through column chromatography (PE:EA=5：1) purify faint yellow Grease (310mg, yield 80%).
1H NMR(400MHz,CDCl3) δ 7.80 (d, J=8.2Hz, 1H), 7.37 (d, J=8.0Hz, 1H), 7.22 (s, 1H), 5.32 (s, 1H), 3.85 (d, J=9.3Hz, 1H), 3.62 (d, J=9.4Hz, 1H), 2.93~2.73 (m, 2H), 2.48 (s, 3H), 1.71 (m, 2H), 1.60 (s, 3H), 1.58 (s, 3H), 1.51~1.30 (m, 6H), 1.20 (s, 3H), 0.91 (s, 3H).13C NMR(101MHz,CDCl3)δ147.84,144.70,1f34.55,133.00,127.92,124.82,72.29, 43.52,38.01,37.39,37.18,37.09,35.02,31.63,29.96,29.71,25.15,21.67,18.80, 18.30,17.14.HRMS(AP-ESI)Calcd.for C20H30NaO:309.2195(M+Na)+.Found:309.2185.
8th, the synthesis of compound 9
Compound 8 (0.11g, 0.40mmol) is dissolved in 1.6ml AcOH, t-BuOOH is sequentially added under stirring at room temperature (115.2 μ L, 1.20mmol) and H2SO4(2.0 μ L, 0.04mmol), is stirred at room temperature 24h.TLC shows and react completely.Rotation is gone molten Agent, is extracted 3 times, organic layer saturation NaHCO with dichloromethane3Washing three times, takes saturation NaHCO again3Layer watery hydrochloric acid adjusts pH To 3, then water layer is extracted twice with dichloromethane, dried, concentration, crude product is through column chromatography (PE:EA=10：1) purify faint yellow Grease (88mg, yield 90%).
1H NMR(400MHz,CDCl3) δ 7.14 (d, J=8.6Hz, 1H), 6.64 (dd, J=8.5,2.7Hz, 1H), 6.53 (d, J=2.6Hz, 1H), 4.77 (s, 1H), 3.02~2.65 (m, 2H), 1.88 (m, 1H) 1.81~1.56 (m, 4H), 1.54~ 1.23(m,4H),1.19(s,3H),0.97(s,3H),0.95(s,3H).13C NMR(300MHz,CDCl3)δ148.12, 138.14,132.15,120.92,110.14,108.16,45.84,36.98,34.31,32.55,28.66,28.59,25.73, 20.23,16.86,14.59,14.25HRMS(AP-ESI)Calcd.for C17H25O:245.1878(M+H)+.Found: 245.1895.
The synthesis of compound 9, peroxidating rearrangement reagent can be H2O2, p-TsOH, t-BuOOH, H2SO4, optimal is t- BuOOH、H2SO4；Solvent can use THF, glacial acetic acid, with glacial acetic acid as optimal；The equivalent of t-BuOOH can be 1eq, 2eq, 3eq, with 3eq is optimal.Result is as shown in table 1.
The synthesis condition of the compound 9 of table 1 is groped
Sequence number Oxidation rearrangement reagent Acid Solvent Yield
1 Hydrogen peroxide (3eq) P-methyl benzenesulfonic acid (0.5eq) Tetrahydrofuran 70%
2 Hydrogen peroxide (2eq) P-methyl benzenesulfonic acid (0.5eq) Glacial acetic acid 46%
3 Hydrogen peroxide (1eq) P-methyl benzenesulfonic acid (0.5eq) Glacial acetic acid 34%
4 Hydrogen peroxide (3eq) P-methyl benzenesulfonic acid (0.5eq) Glacial acetic acid 79%
5 Tertbutanol peroxide (3eq) The concentrated sulfuric acid (0.1eq) Glacial acetic acid 90%
6 Tertbutanol peroxide (2eq) The concentrated sulfuric acid (0.1eq) Glacial acetic acid 55%
7 Tertbutanol peroxide (1eq) The concentrated sulfuric acid (0.1eq) Glacial acetic acid 48%
8 Tertbutanol peroxide (3eq) The concentrated sulfuric acid (0.1eq) Tetrahydrofuran 79%
The syntheti c route of the compound 8 of comparative example 1
Inventor explores the syntheti c route of a plurality of compound 8, and a syntheti c route therein is as follows：
(a) 33%HBr/AcOH, rt., 6h, 88%；(b) LiOH, N,N-dimethylformamide, 80 DEG C, 7h, 100%； (c)SeO2, tetrahydrofuran, 0 DEG C, 5h, 80%；(d)EtI,K2CO3, acetone, 60 DEG C, 3h, 92%；(e)LiAlH4, tetrahydrochysene furan Mutter, rt., 3h, 84%；(f) PCC drone salt, dichloromethane, rt., 4h, 90%.
Specially：
The synthesis of compound 2：Rosin acid 1 is dissolved in solvent, hydrogen bromide, rosin acid is added：The mol ratio of hydrogen bromide It is 1:2, in stirring reaction 5h~7h under normal temperature, filtering is washed with the glacial acetic acid of icing shape, is vacuum dried 12 hours after washing, Obtain intermediate 2；
The synthesis of compound 3：To be obtained in step (a) intermediate 2 is dissolved in solvent, alkali is added at normal temperatures, it is middle Body 2 is 1 with hydroxide ion mol ratio:2.5,80 DEG C of stirring reaction 4h~6h are warming up to, plus pH is adjusted to 2~3, extraction by watery hydrochloric acid Take, wash, concentrate, obtain intermediate 3；
The synthesis of compound 10：To be obtained in step (b) intermediate 3 is dissolved in solvent, 0 DEG C stir under add dioxy Change selenium, intermediate 3:The mol ratio of selenium dioxide is 1:Constant temperature stirring reaction 4h~12h, filters, extracts, washes at 2~8,0 DEG C Wash, concentrate, obtain intermediate 4；
The synthesis of compound 11：To be obtained in step (c) intermediate 4 is dissolved in acetone, add alkali under stirring at normal temperature, Stir 15 minutes, adding iodoethane, intermediate 10：The mol ratio of iodoethane is 1:2,60 DEG C of reaction 4h~6h are warming up to, Extraction, washing, concentration, obtain rosin acid derivative 11；
The synthesis of compound 12：The intermediate 11 that step (d) is obtained tetrahydrofuran dissolves, and is added under ice bath stirring To in the tetrahydrofuran mixed liquor of Lithium Aluminium Hydride, intermediate 4：The mol ratio of Lithium Aluminium Hydride is 1:4, reaction 3h is stirred at room temperature, adjust PH to 6, filtering, extraction, washing, concentration, obtains rosin acid derivative 12；
The synthesis of compound 13：The intermediate 12 and pyridinium chloro-chromate for respectively being obtained step (e) with dichloromethane Dissolving, intermediate is 1 with the mol ratio of pyridinium chloro-chromate:By the dichloromethane solution of intermediate 12 under 1.5,25 DEG C of stirrings Dropwise it is added drop-wise to during pyridinium chloro-chromate obtains dichloromethane solution, stirring at normal temperature reaction 4h, filtering, extraction, washing is dried, Concentration, purifies to obtain rosin acid derivative 13.
But in building-up process, 140 points of difficulties of compound are synthesized from compound 13.During using Huang Min-lon reduction, raw material Completely, but point is very miscellaneous without obvious principal point for 13 fundamental reactions, and reaction temperature is close to the boiling point of dimethicone.Therefore, should Bar route is not suitable for the preparation of compound 8.
The syntheti c route of the compound 8 of comparative example 2
Inventor explores the syntheti c route of a plurality of compound 8, and a syntheti c route therein is as follows：
(a)EtI,K2CO3, acetone, 60 DEG C, 3h, 94%；(b)LiAlH4, THF, rt., 3h, 84%；(c) TsCl, pyridine, Rt, 5h, 84%；(d) Zn, NaI, HMPA, 105 DEG C, 6h, 98%.
The synthesis of compound 15：Rosin acid 1 is dissolved in acetone, alkali is added under stirring at normal temperature, stirred 15 minutes, Add iodoethane, intermediate 10：The mol ratio of iodoethane is 1:2,60 DEG C of reaction 4h~6h are warming up to, extract, wash, concentrate, Obtain rosin acid derivative 15；
The synthesis of compound 16：The intermediate 15 that step (a) is obtained tetrahydrofuran dissolves, and is added under ice bath stirring To in the tetrahydrofuran mixed liquor of Lithium Aluminium Hydride, intermediate 15：The mol ratio of Lithium Aluminium Hydride is 1:4, reaction 3h is stirred at room temperature, adjust PH to 6, filtering, extraction, washing, concentration, obtains rosin acid derivative 16；
The synthesis of compound 17：The intermediate 16 and paratoluensulfonyl chloride pyridinium dissolution that step (b) is obtained, intermediate 16 is 1 with the mol ratio of paratoluensulfonyl chloride:5, reaction 5h is stirred at room temperature.Pyridine is removed in rotation, and extraction, washing, concentration, column chromatography are pure Change to obtain rosin acid derivative 17；
The synthesis of compound 18：The intermediate 17 that step (c) is obtained HMPA dissolves, and is added dropwise to In sodium iodide and zinc powder, 105 DEG C of stirring reaction 6h are warming up to.With petroleum ether extraction, dry, concentration, column chromatography purifies to obtain rosin Acid derivative 18；
The synthesis of compound 19：The intermediate 18 that step (d) is obtained is dissolved in glacial acetic acid, and 33% bromination is added dropwise under ice bath The glacial acetic acid solution of hydrogen, is stirred at room temperature, the reaction impurities showed increased when inventory is amplified, and causes product molten from glacial acetic acid Precipitation in liquid, and the equal very little of polarity of product, unreacting material and impurity, the purifying to product become very difficult, yield pole It is low.Therefore, this route is not suitable for the preparation of compound 8.
The bioactivity of test example the compounds of this invention
Using the PTP1B recombinant proteins (Sigma) of purchase, with 4-NPP (pNPP) for substrate is detected PTP1B activity.The positive reference compound for using is oleanolic acid.The phosphoric acid ester bond of substrate nNPP can be hydrolyzed using PTP1B, is obtained To product p-nitrophenol have very strong light absorbs at 410nm in the basic conditions, inhaled by light at direct detection 410nm The change of receipts is to observe suppression situation of the compound to enzymatic activity, and concrete operation method is as follows：By the μ of the aqueous solution 48 of substrate pNPP μ L of L, PTP1B cushioning liquid 50 (25Mm HEPES, PH 7.2,1MmEDTA, 1.5Mm DTT, 50Mm NaCl), compound The μ L of DMSO solution 2 sequentially add the reaction system that 100 μ L are constituted in 96 orifice plates.After 37 DEG C of reaction 30min, 5 μ L 1N are added per hole The NaOH aqueous solution, absorbance is surveyed at 410nm using EnSpire ELIASAs.In the reaction solution without testing compound, Absorbance (At) is defined as 100% activity.In the reaction solution without PTP1B, absorbance (Ab) is defined as 0% activity.For Testing compound, inhibiting rate (%)=[1- (A-Ab)/(At-Ab)] × 100, wherein A is the reaction solution containing testing compound Absorbance.
PTP1B inhibiting rate of the compound of table 2 under 100 μM of concentration
Using oleanolic acid OA as positive control, the PTP1B inhibitory activity of the rosin acid derivative to synthesizing is measured. Inhibiting rates of the corresponding PTP1B of compound under 100 μM of concentration is as shown in table 1.Experimental data shows, a series of synthesized pines It is most of that all there is certain PTP1B inhibitory activity in fragrant acid derivative.By interpretation structure-activity relationship, can obtain Go out to draw a conclusion：When C-4 of rosin acid derivative for carboxyl, terpene skeleton part is carried out into aromatization, introduce hydroxyl or The tert-butyl alcohol, the compound PTP1B inhibitory activity for introducing the tert-butyl alcohol is more preferable；And when the carboxyl of C-4 is changed into gem-dimethyl, terpene Class skeleton aromatization simultaneously, phenolic hydroxyl-compounds are good compared with tert-butyl alcohol compound inhibitory activity；When the terpene bone of rosin acid derivative Frame part keeps constant, and the C-4 change of group be not obvious for the influence of compound inhibitory activity.

Claims (10)

1. compound shown in a kind of prepare compound 8, or its pharmaceutically acceptable salt, or its solvate method, it is special Levy and be：The described method comprises the following steps：
(1) compound 1 is converted into compound 5；
(2) compound 5 is converted into compound 8.
2. method according to claim 1, it is characterised in that：The step (1) comprises the following steps：
A, by compound 1 and reaction of hydrogen bromide, prepare compound 2；
B, under alkaline environment, compound 2 is converted into compound 3；
C, compound 3 is converted into compound 4；
D, compound 4 is converted into compound 5.
3. method according to claim 2, it is characterised in that：In the step a, solvent is acetic acid, preferred reaction temperature Spend is 20~30 DEG C.
4. method according to claim 2, it is characterised in that：In the step b, alkali used is LiOH, and solvent is two NMF；Preferred reaction temperature is 80 DEG C.
5. method according to claim 2, it is characterised in that：In the step c, including compound 3 and iodoethane are existed The step of being reacted under alkaline environment；Preferably, alkali used is potassium carbonate, and solvent is acetone；Further preferred reaction temperature It is 60 DEG C.
6. method according to claim 2, it is characterised in that：In the step d, including by compound 4 and LiAlH4Reaction The step of；Preferably, solvent is tetrahydrofuran；Further preferred reaction temperature is 20~30 DEG C.
7. method according to claim 1, it is characterised in that：The step (2) comprises the following steps：
E, compound 5 is converted into compound 6；
F, compound 6 is converted into compound 7；
G, compound 7 is converted into compound 8.
8. method according to claim 7, it is characterised in that：In the step e, including by compound 5 with to methylbenzene The step of sulfonic acid chloride reacts；Preferably, described solvent is selected from dichloromethane, pyridine, tetrahydrofuran, acetonitrile, more preferably pyridine； Further preferred reaction temperature is 20~30 DEG C.
9. method according to claim 7, it is characterised in that：In the step f, including by compound 6 and sodium iodide and The step of zinc powder reacts；Preferably, described solvent is selected from DMF, dimethyl sulfoxide, HMPA, It is preferred that HMPA；Further preferred reaction temperature is 105 DEG C.
10. method according to claim 7, it is characterised in that：In the step g, including by compound 7 and SeO2Reaction The step of；Preferred solvent is selected from dichloromethane, tetrahydrofuran, acetonitrile, more preferably tetrahydrofuran；Further preferred reaction temperature Spend is 0 DEG C.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104370745A (en) * 2014-10-17 2015-02-25 西华大学 Preparation method of abietic acid derivatives
CN105001049A (en) * 2015-06-03 2015-10-28 西华大学 Preparation method for abietic acid derivative

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104370745A (en) * 2014-10-17 2015-02-25 西华大学 Preparation method of abietic acid derivatives
CN105001049A (en) * 2015-06-03 2015-10-28 西华大学 Preparation method for abietic acid derivative

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Application publication date: 20170613