CN117924168A - Synthesis method of carbamazepine intermediate 6-quinoline propanal - Google Patents
Synthesis method of carbamazepine intermediate 6-quinoline propanal Download PDFInfo
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- CN117924168A CN117924168A CN202311735026.6A CN202311735026A CN117924168A CN 117924168 A CN117924168 A CN 117924168A CN 202311735026 A CN202311735026 A CN 202311735026A CN 117924168 A CN117924168 A CN 117924168A
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- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 title claims abstract description 24
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 229960000623 carbamazepine Drugs 0.000 title claims abstract description 18
- 238000001308 synthesis method Methods 0.000 title claims description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 14
- GKJSZXGYFJBYRQ-UHFFFAOYSA-N 6-chloroquinoline Chemical compound N1=CC=CC2=CC(Cl)=CC=C21 GKJSZXGYFJBYRQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 10
- WMDHQEHPOVOEOG-UHFFFAOYSA-N 2-(2-bromoethyl)-1,3-dioxane Chemical compound BrCCC1OCCCO1 WMDHQEHPOVOEOG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000005859 coupling reaction Methods 0.000 claims abstract description 9
- 238000010511 deprotection reaction Methods 0.000 claims abstract description 9
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- LZKLAOYSENRNKR-LNTINUHCSA-N iron;(z)-4-oxoniumylidenepent-2-en-2-olate Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LZKLAOYSENRNKR-LNTINUHCSA-N 0.000 claims abstract description 7
- 239000002841 Lewis acid Substances 0.000 claims abstract description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 6
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 4
- 239000011777 magnesium Substances 0.000 claims abstract description 4
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 3
- VUAOIXANWIFYCU-UHFFFAOYSA-N quinoline-6-carbaldehyde Chemical compound N1=CC=CC2=CC(C=O)=CC=C21 VUAOIXANWIFYCU-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001299 aldehydes Chemical class 0.000 claims 1
- 229910000510 noble metal Inorganic materials 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LIOLIMKSCNQPLV-UHFFFAOYSA-N 2-fluoro-n-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1C1=NN2C(CC=3C=C4C=CC=NC4=CC=3)=CN=C2N=C1 LIOLIMKSCNQPLV-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- IFIHYLCUKYCKRH-UHFFFAOYSA-N 6-bromoquinoline Chemical compound N1=CC=CC2=CC(Br)=CC=C21 IFIHYLCUKYCKRH-UHFFFAOYSA-N 0.000 description 1
- GSCCALZHGUWNJW-UHFFFAOYSA-N N-Cyclohexyl-N-methylcyclohexanamine Chemical compound C1CCCCC1N(C)C1CCCCC1 GSCCALZHGUWNJW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229950005852 capmatinib Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- DOKHEARVIDLSFF-UHFFFAOYSA-N prop-1-en-1-ol Chemical compound CC=CO DOKHEARVIDLSFF-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- -1 tri-tert-butylphosphonium tetrafluoroborate Chemical compound 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a method for synthesizing a carbamazepine intermediate 6-quinoline propanal, which sequentially comprises a format reaction, a coupling reaction and a deprotection reaction, wherein 2- (2-bromoethyl) -1, 3-dioxane is used as a reaction reagent, and the format reaction is carried out with magnesium scraps in tetrahydrofuran or an aprotic solvent to obtain a format reagent; performing coupling reaction with a format reagent by taking 6-chloroquinoline as a reagent and Fe (acac) 3 as a catalyst to obtain acetal; and (3) carrying out deprotection reaction on Lewis acid serving as a reaction reagent and acetal in a proton solvent to obtain the 6-quinoline propanal. The raw materials adopted by the invention are cheap and easy to obtain the 6-chloroquinoline and the 2- (2-bromoethyl) -1, 3-dioxane, the synthetic route is simple in process, mild in reaction condition, safe in operation, high in average yield and purity of the product, free of noble metal catalyst, low in cost and suitable for large-scale industrial production.
Description
Technical Field
The invention belongs to the field of synthesis of drug intermediates, and particularly relates to a method for synthesizing a carbamazepine intermediate 6-quinoline propanal.
Background
Carmattinib (English name: capmatinib), molecular formula C 23H17FN6 O, its structural formula isCAS number 1029712-80-8, wherein 6-quinolinecarboxaldehyde and analogues thereof are pharmaceutical intermediates for the preparation of carbamazepine, the synthetic technical route of which mainly comprises:
The characteristics are as follows: the three-step reaction requires two-step Pd catalyst, has high material cost, and has one-step oxidation in the middle, and has high cost and difficulty (reference document: ASTELLAS PHARMAINC. -EP1396490,2004, A1).
The characteristics are as follows: one-step reaction, but using Pd catalysis, the material cost is high and propenol is not readily available (ref: INCYTE CORP-WO2008/64157,2008, A1).
The characteristics are as follows: two-step reactions, but using Pd catalysis in both steps, are costly (ref: INCYTE CORP-US 2009/291496, 2009, A1).
In summary, the reaction process conditions of the method for synthesizing the carbamazepine intermediate 6-quinoline propanal in the prior art are harsh, the equipment requirements are high, a noble metal catalyst or a non-readily available raw material is needed, and the economic efficiency is poor.
Disclosure of Invention
Aiming at the defects in the prior art, the invention mainly aims to provide a method for synthesizing a carbamazepine intermediate 6-quinoline propanal, which solves the problems that the existing synthesis method has harsh reaction process conditions and needs to adopt a noble metal catalyst or a non-readily available raw material.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the invention provides a method for synthesizing a carbamazepine intermediate 6-quinoline propanal, which comprises the following technical routes:
Comprising the following steps: step1 is a format reaction; step2 is a coupling reaction; step3 is a deprotection reaction; specifically, the preparation method comprises the following steps:
(1) 2- (2-bromoethyl) -1, 3-dioxane is used as a reaction reagent, and is subjected to format reaction with magnesium scraps in tetrahydrofuran or an aprotic solvent to obtain a format reagent shown in a formula I;
(2) Performing coupling reaction with a reagent in a format of formula I by taking 6-chloroquinoline as a reagent and Fe (acac) 3 as a catalyst to obtain acetal shown in a formula II;
(3) And (3) carrying out deprotection reaction on Lewis acid serving as a reaction reagent and the acetal in a proton solvent to obtain the 6-quinoline propanal.
Preferably, in the step (1), the molar ratio of the magnesium chips to the 2- (2-bromoethyl) -1, 3-dioxane is 6:1.
Preferably, in the step (1), the reaction temperature of the format reaction is 0-10 ℃ and the reaction time is 0.5-2h.
Preferably, in step (2), the molar ratio of Fe (acac) 3, 6-chloroquinoline and formazan reagent is from 0.2 to 0.8:4:5, more preferably 0.6:4:5.
Preferably, in the step (2), the reaction temperature of the coupling reaction is 20-30 ℃ and the reaction time is 2-3 h.
Preferably, the lewis acid of step (3) is selected from dilute hydrochloric acid or dilute sulfuric acid.
More preferably, in step (3), the lewis acid is selected from dilute sulfuric acid, and the mass-to-volume ratio of the acetal to the dilute sulfuric acid is 1:10 (g/mL).
Preferably, in the step (3), the reaction temperature of the deprotection reaction is 15-25 ℃ and the reaction time is 4-5 h.
Compared with the prior art, the invention has the following beneficial effects:
The invention provides a novel method for synthesizing a carbamazepine intermediate 6-quinoline propanal, which adopts a large amount of raw materials such as 6-chloroquinoline and 2- (2-bromoethyl) -1, 3-dioxane, has the advantages of low cost, easy obtainment, simple synthesis route process, mild reaction conditions, safe operation, simple post-treatment process, easy purification of crude products without complex modes such as column chromatography, average yield of more than 80 percent, purity of more than 95.0 percent, no need of noble metal catalyst, low cost and suitability for large-scale industrial production.
Drawings
FIG. 1 is a representation of the synthesis of 6-quinolinecarboxaldehyde in the examples.
Detailed Description
The present invention will be described in further detail by way of examples, but the present invention is not limited to these examples.
The experimental procedure, in which specific conditions are not noted in the examples below, is generally followed by conventional conditions.
Comparative example 1
This comparative reference INCYTE CORP-WO2008/64157,2008, a1 prepared 6-quinolinecarbaldehyde by the following technical route:
The flask was evacuated and refilled with nitrogen (2 times) with tris (dibenzylideneacetone) dipalladium (480 mg,0.52 mmol) and tri-tert-butylphosphonium tetrafluoroborate (300 mg,1.0 mmol). 1, 4-Dioxane (31 mL) was added followed by the successive addition of 6-bromoquinoline (7.2 g,35 mmol), 2-propen-1-ol (4.7 mL,69 mmol) and N-cyclohexyl-N-methylcyclohexylamine (8.9 mL,42 mmol). The reaction vessel was evacuated and refilled with nitrogen (2 times), the reaction mixture was stirred at 30 ℃ for 24 hours, diethyl ether (30 mL) was added to the reaction mixture, followed by filtration and washing with diethyl ether, and the organic extract was concentrated under reduced pressure. The residue was purified by flash chromatography eluting with ethyl acetate in hexane (0-50%) to give the desired product.
Example 1
The preparation of the target 6-quinolinecarboxaldehyde (CAS number 476660-18-1) in this example is the following scheme:
step1:
Into a 2L reaction flask was charged magnesium turnings (51.8 g, 3.6 eq), THF (600 mL,5.1 v/w), stirring was turned on, and nitrogen was replaced 2 times; then controlling the internal temperature to be 20 ℃, dropwise adding 2- (2-bromoethyl) -1, 3-dioxane (17.0 g, about 15% of the total amount), stirring for 20min, and naturally raising the internal temperature to about 55 ℃ (judging that the format is successfully initiated); finally, cooling to 0-10 ℃ in ice bath, dropwise adding the rest 2- (2-bromoethyl) -1, 3-dioxane (100 g), stirring for about 1h at 0-10 ℃ after the completion of the dropwise adding, preserving heat at 0-10 ℃, and standing for later use;
step2:
THF (400 mL,10 v/w), fe (acac) 3 (13 g,0.15 eq) and NMP (284 g,12.0 eq) were added to a 3L reaction flask at room temperature (25-30deg.C), stirring was turned on, and 6-chloroquinoline (40 g,1.0 eq) was added; nitrogen is replaced for 2 times; the temperature in the reaction bottle is controlled to be 20-30 ℃, a step1 self-made format reagent (equal to 660mL,2.5 eq) is dripped into the reaction bottle, and the reaction bottle is stirred for 2-3 h; TLC detection, wherein the 6-chloroquinoline completely reacts; dropping the reaction liquid into saturated ammonium chloride solution (450 mL), controlling the temperature to be 0-15 ℃, and stirring for 30min; standing for layering, and washing the organic phase once again by using saturated ammonium chloride solution (200 mL); the aqueous phases were combined, extracted once with EA (500 mL), the organic phases combined, dried over anhydrous sodium sulfate, and concentrated to 67g of compound ii, HPLC purity: 96.1%;
step3:
Step2 is weighed into a 100mL reaction bottle to prepare a compound II (1.5 g), 2.5% H 2SO4 (15 mL) is added, and the mixture is stirred for 4 to 5 hours at 20+/-5 ℃; sampling HPLC detection reaction is complete; EA (30 ml×2) was added for extraction, the organic phase was discarded, the aqueous phase was adjusted to ph=8-9 with saturated Na 2CO3 solution, and EA (30 ml×2) was added for extraction; the organic phase obtained is treated after the reaction, activated carbon (0.4 g) is added, stirred and decolorized for 1h, filtered and concentrated to obtain 0.7g of light brown oily substance with HPLC purity: 89.5%.
The HNMR characterization of the 6-quinolinecarboxaldehyde prepared in example 1 is shown in FIG. 1.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (9)
1. The synthesis method of the carbamazepine intermediate 6-quinoline propanal is characterized by comprising the following technical routes:
wherein Step1 is a formal reaction; step2 is a coupling reaction; step3 is a deprotection reaction;
the preparation method comprises the following steps:
(1) Format reaction: 2- (2-bromoethyl) -1, 3-dioxane is used as a reaction reagent, and is subjected to format reaction with magnesium scraps in tetrahydrofuran or an aprotic solvent to obtain a format reagent shown in a formula I;
(2) Coupling reaction: performing coupling reaction with a reagent in a format of formula I by taking 6-chloroquinoline as a reagent and Fe (acac) 3 as a catalyst to obtain acetal shown in a formula II;
(3) Deprotection reaction: and (3) carrying out deprotection reaction on Lewis acid serving as a reaction reagent and the acetal in a proton solvent to obtain the 6-quinoline propanal.
2. The method for synthesizing a carbamazepine intermediate 6-quinolinecarboxaldehyde according to claim 1, wherein in the step (1), the molar ratio of magnesium turnings to 2- (2-bromoethyl) -1, 3-dioxane is 6:1.
3. The method for synthesizing the carbamazepine intermediate 6-quinolinecarboxyl aldehyde according to claim 1, wherein in the step (1), the reaction temperature of the format reaction is 0-10 ℃ and the reaction time is 0.5-2 h.
4. The method for synthesizing the carbamazepine intermediate 6-quinolinecarboxaldehyde according to claim 1, wherein in the step (2), the molar ratio of Fe (acac) 3, 6-chloroquinoline and the formative reagent is 0.2-0.8:4:5.
5. The method for synthesizing the carbamazepine intermediate 6-quinolinecarboxaldehyde according to claim 4, wherein the molar ratio of Fe (acac) 3, 6-chloroquinoline and formative reagent is 0.6:4:5.
6. The method for synthesizing the carbamazepine intermediate 6-quinolinecarboxaldehyde according to claim 1, wherein in the step (2), the reaction temperature of the coupling reaction is 20-30 ℃ and the reaction time is 2-3 h.
7. The method for synthesizing a carbamazepine intermediate 6-quinolinecarboxaldehyde according to claim 1, wherein said lewis acid of step (3) is selected from the group consisting of dilute hydrochloric acid and dilute sulfuric acid.
8. The method for synthesizing a carbamazepine intermediate 6-quinolinecarboxaldehyde according to claim 7, wherein in the step (3), the mass-to-volume ratio of the acetal to the dilute sulfuric acid is 1:10 (g/mL).
9. The method for synthesizing the carbamazepine intermediate 6-quinolinecarboxaldehyde according to claim 1, wherein in the step (3), the reaction temperature of the deprotection reaction is 15-25 ℃, and the reaction time is 4-5 h.
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