CN112645839A - Bilateral asymmetric substituent substituted tartaric acid skeleton compound and application thereof - Google Patents
Bilateral asymmetric substituent substituted tartaric acid skeleton compound and application thereof Download PDFInfo
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- 230000002146 bilateral effect Effects 0.000 title claims abstract description 29
- -1 tartaric acid skeleton compound Chemical class 0.000 title claims abstract description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 20
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 20
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 229940126214 compound 3 Drugs 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 13
- 229940125782 compound 2 Drugs 0.000 claims description 11
- 229940125898 compound 5 Drugs 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 claims description 10
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 10
- 235000002906 tartaric acid Nutrition 0.000 claims description 10
- 239000011975 tartaric acid Substances 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 7
- 238000004440 column chromatography Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 6
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 claims description 6
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 3
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 150000003892 tartrate salts Chemical class 0.000 claims 4
- 239000012450 pharmaceutical intermediate Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 17
- 239000003814 drug Substances 0.000 abstract description 16
- 229940079593 drug Drugs 0.000 abstract description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 4
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 abstract description 4
- 125000004185 ester group Chemical group 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 4
- 238000006467 substitution reaction Methods 0.000 abstract description 4
- 230000018044 dehydration Effects 0.000 abstract description 2
- 238000006297 dehydration reaction Methods 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000003899 tartaric acid esters Chemical class 0.000 description 3
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical group OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/24—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to carbon atoms of six-membered aromatic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a tartaric acid skeleton compound substituted by bilateral asymmetric substituent groups, which has the following structure:
Description
Technical Field
The invention relates to the field of chiral compound preparation, in particular to a bilateral asymmetric substituent substituted tartaric acid skeleton compound and application thereof.
Background
The chiral compound has wide application value in the fields of drug synthesis and asymmetric catalysis. The common method for introducing chiral factors in the synthesis of chiral drug intermediates is to introduce a natural chiral skeleton, and tartaric acid is one of the common natural chiral skeletons. However, most of chiral tartaric acid and derivatives thereof are symmetrically substituted derivatives on the functional group substitution, and the main reason is that the synthesis difficulty of symmetric substitution is low in the structural modification process of chiral tartaric acid, and the ee value of the obtained final product is high.
However, the chiral tartaric acid and the derivatives thereof which are symmetrically substituted are usually limited to the preparation of chiral compound intermediates with symmetry in the process of preparing chiral drugs, and most molecules of chiral drug structures are usually asymmetric drug molecular structures in the natural world, especially in the process of synthesizing natural drugs, and the tartaric acid and the derivatives thereof which are modified by the symmetric structures can not be applied to the synthesis process of chiral drug molecules under the conditions.
The reasons for the technical bottlenecks are as follows: in the prior art, the method for asymmetrically modifying the tartaric acid skeleton is rare, and the specific reasons are as follows:
1. a suitable substituent compound which can be symmetrically substituted cannot be found;
2. the synthesis process has greater difficulty;
3. the development of synthetic routes is difficult;
4. the obtained symmetric tartaric acid skeleton compound needs to be screened in the actual chiral drug synthesis application process.
Disclosure of Invention
The invention aims to solve the technical problem of providing a tartaric acid skeleton compound substituted by bilateral asymmetric substituent groups.
The invention solves the technical problems through the following technical scheme:
a bilateral asymmetric substituent substituted tartaric acid skeleton compound has the following structure:
preferably, the synthetic general formula of the bilateral asymmetric substituent substituted tartaric acid skeleton compound is as follows:
preferably, the preparation method of the bilateral asymmetric substituent substituted tartaric acid skeleton compound comprises the following steps:
(1) preparation of compound 2:
respectively adding a compound 1 and acetone serving as solvents into a round-bottom flask, dropwise adding boron trifluoride diethyl etherate into the mixture in an ice bath, heating to room temperature after dropwise adding, stirring for 12, and separating and purifying to obtain a compound 2;
(2) preparation of compound 3:
respectively adding the compound 2 prepared in the step (1), water and 1, 4-dioxane into a round-bottom flask, dropwise adding a sodium hydroxide solution into the mixture, stirring at room temperature, adding hydrochloric acid into the reaction system, adjusting the pH value to 1-2, and separating and purifying to obtain a compound 3;
(3) preparation of compound 4:
respectively adding a compound 3, N-methylaniline, 1-hydroxybenzotriazole, (3mmol) 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N, N' -dimethylformamide into a round-bottom flask, stirring the mixture at room temperature, and separating and purifying to obtain a compound 4;
(4) preparation of compound 5:
respectively adding a compound 4 and 1, 3-propane diamine into a round-bottom flask, stirring the reaction system at room temperature, and separating and purifying the reaction system to obtain a compound 5;
(5) preparation of compound 6:
respectively adding a compound 5, trifluoroacetic acid and water into a round-bottom flask, stirring at room temperature, concentrating to dryness, adding salicylaldehyde and ethanol into the concentrated system, dropwise adding triethylamine, adjusting to alkalescence, stirring at room temperature for reaction, concentrating the reaction system to dryness, and separating and purifying to obtain a compound 6, wherein the compound 6 is a bilateral asymmetric substituent substituted tartaric acid skeleton compound.
Preferably, the molar ratio of the compound 1 to the boron trifluoride diethyl etherate in the step (1) is 1: 1.2.
Preferably, the molar ratio of the compound 2 in the (2) to the sodium hydroxide in the sodium hydroxide solution is 1: 1.04.
Preferably, the molar ratio of the compound 3 to the N-methylaniline in the (3) is 1: 1.5;
the molar ratio of the compound 3 to the 1-hydroxybenzotriazole in the step (3) is 1: 1.5;
the molar ratio of the compound 3 to the 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride in the (3) is 1: 1.5.
Preferably, the molar ratio of the compound 5 to the salicylaldehyde in the step (5) is 1: 1.2.
Preferably, the separation and purification in the steps (1) to (5) comprise column chromatography.
The invention also discloses application of the bilateral asymmetric substituent substituted tartaric acid skeleton compound in synthesis of chiral drug intermediates.
Compared with the prior art, the invention has the following advantages:
1. the invention discloses an asymmetrically substituted tartaric acid derivative, which realizes the provision of a reaction substance of the asymmetrically substituted tartaric acid derivative in the synthesis of an asymmetric chiral drug molecule;
2. the invention solves the synthesis technical bottleneck of preparing the asymmetrically substituted tartaric acid derivative in the prior art;
3. the reactant which can be applied to asymmetric chiral drug molecule synthesis is obtained by screening, so that high-efficiency synthesis possibility is provided for asymmetric chiral drug molecule synthesis, and the difficulty in asymmetric chiral drug molecule synthesis is reduced.
Drawings
FIG. 1 is an H-NMR spectrum of Compound 2 obtained by the preparation in example 4 of the present invention;
FIG. 2 is an H-NMR spectrum of Compound 3 obtained in example 4 of the present invention;
FIG. 3 is an H-NMR spectrum of Compound 4 obtained by the preparation in example 4 of the present invention;
FIG. 4 is an H-NMR spectrum of Compound 5 obtained in example 4 of the present invention;
FIG. 5 is an H-NMR spectrum of compound 6 obtained by the production in example 4 of the present invention.
Detailed Description
The following examples are given for the detailed implementation and specific operation of the present invention, but the scope of the present invention is not limited to the following examples.
EXAMPLE 1 bilateral asymmetric substituent substituted tartaric acid backbone Compounds
This example discloses a compound with a structure of a bilateral asymmetric substituent substituted tartaric acid skeleton as shown above, which can be clearly obtained from the structure:
on the skeleton structure of tartaric acid, a group introduced on a mother nucleus group at one side is N-methylphenyl, and a group introduced on the other side is a phenol derivative substituent which has a more obvious structural difference with the N-methylphenyl.
Example 2 synthetic route to bilateral asymmetric substituent substituted tartaric acid backbone compounds
The synthetic route of the compound with the tartaric acid skeleton substituted by bilateral asymmetric substituent groups is as follows:
from the synthetic route, it follows that:
the compound 1 is used as a substrate, and a target product is obtained by condensation, hydrolysis of unilateral ester groups to form carboxyl, introduction of N-methylphenyl by carboxyl dehydration, introduction of aliphatic amine by heteroside ester group substitution, and condensation of the aliphatic amine and salicylaldehyde.
Example 3 synthetic route for bilateral asymmetric substituent substituted tartaric acid backbone compounds
Example 4 Synthesis of a Compound having a tartaric acid backbone substituted with bilateral asymmetric substituents
(1) To a 100mL round-bottomed flask were added 3.4mL (20mmol) of Compound 1((2R,3S) -diethyl-2, 3-dihydroxysuccinate) and 36mL of acetone, respectively, and to the above mixture was added dropwise 3.0mL (24mmol) of boron trifluoride ether solution under ice bath. After the addition was complete, the temperature was raised to room temperature and stirred for 12 hours. Adding 50mL of saturated sodium bicarbonate solution into the reaction system, extracting with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, concentrating the organic phase to dryness, and carrying out column chromatography on a crude product, wherein an eluent is petroleum ether: ethyl acetate 10:1 (V/V). 3.9g of Compound 2((4R,5S) -diethyl-2, 2-dimethyl-1, 3-dioxolane-4, 5-dicarbonate) are obtained in a yield of 80%, 98.2% ee.
(2): to a 250mL round-bottom flask were added 3.9g of Compound 2, 40mL of water, and 40mL of 1, 4-dioxane, respectively, and 16.4mL of a 1mol/L sodium hydroxide solution was added dropwise to the above mixture, and stirred at room temperature for 4 hours. Adding 1mol/L hydrochloric acid into the reaction system, adjusting the pH value to be 1-2, extracting the mixture with 200mL dichloromethane for three times, drying an organic phase with anhydrous sodium sulfate, concentrating the organic phase to be dry, and performing column chromatography separation on a crude product, wherein an eluent is dichloromethane: methanol 10:1 (V/V). 2.7g of Compound 3 ((4R,5S) -5-ethoxycarbonyl-2, 2-dimethyl-1, 3-dioxolane-4-carboxylic acid) are obtained in 79% yield and 98.5% ee.
(3): to a 100mL round-bottom flask were added 0.44g (2mmol) of Compound 3, 0.33g (3mmol) of N-methylaniline, 0.4g (3mmol) of 1-hydroxybenzotriazole, 0.58g (3mmol) of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and 30mL of N, N' -dimethylformamide, respectively, and the mixture was stirred at room temperature for 12 hours, then washed three times with 100mL of water, and extracted with ethyl acetate. Drying the organic phase by using anhydrous sodium sulfate, concentrating the organic phase to be dry, and carrying out column chromatography separation on a crude product, wherein an eluent is petroleum ether: ethyl acetate 5:1 (V/V). 0.53g of compound 4((4R,5S) -ethyl-2, 2-dimethyl-5- (methylphenylcarbamoyl) -1, 3-dioxolan-4-yl) is obtained in 86% yield and 98% ee.
(4): to a 10mL round-bottom flask were added 0.25g (0.8mmol) of Compound 4 and 5mL of 1, 3-propanediamine, respectively, and the above reaction was stirred at room temperature for 1 hour. Concentrating the reaction system to dryness, and performing column chromatography separation on a crude product, wherein an eluent is dichloromethane: methanol 10:1 (V/V). 0.28g of Compound 5 ((4R,5S) -N4- (3-aminopropyl) -N5,2, 2-tertiary and-N5-phenyl-1, 3-dioxolane-4, 5-dicarboxamide) is obtained in a yield of 99%, 98.8%.
(5): to a 10mL round-bottom flask were added 0.067g (0.2mmol) of Compound 5, 4.5mL of trifluoroacetic acid, and 0.5mL of water, respectively, and the mixture was stirred at room temperature for 12 hours and then concentrated to dryness. To the above system, 0.025 mL (0.24mmol) of salicylaldehyde and 5mL of ethanol were added, triethylamine was added dropwise, and pH was adjusted to 8, followed by stirring at room temperature for 12 hours. Concentrating the reaction system to dryness, and performing column chromatography separation on a crude product, wherein an eluent is dichloromethane: methanol 10:1 (V/V). 0.22g of compound 6((4R,5S) -N4- (3-Z- (2-hydroxybenzylidene) aminopropyl-N5, 2, 2-trimethyl-N5-phenyl-1, 3-dioxolane-4, 5-dicarboxamide) is obtained in a yield of 85% 97.6% ee.
The compound 6 is a compound with a tartaric acid skeleton substituted by bilateral asymmetric substituents.
The H-NMR spectra of the above compounds 2 to 6 are shown in FIGS. 1 to 5.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (9)
1. The bilateral asymmetric substituent substituted tartaric acid skeleton compound is characterized in that the structure is shown as follows
2. The bilateral asymmetric substituent-substituted tartaric acid backbone compound of claim 1, wherein the bilateral asymmetric substituent-substituted tartaric acid backbone compound is synthesized according to the general formula:
3. the bilateral asymmetric substituent-substituted tartaric acid backbone compound of claim 2, wherein the bilateral asymmetric substituent-substituted tartaric acid backbone compound is prepared by a method comprising the steps of:
(1) preparation of compound 2:
respectively adding a compound 1 and acetone serving as solvents into a round-bottom flask, dropwise adding boron trifluoride diethyl etherate into the mixture in an ice bath, heating to room temperature after dropwise adding, stirring for 12, and separating and purifying to obtain a compound 2;
(2) preparation of compound 3:
respectively adding the compound 2 prepared in the step (1), water and 1, 4-dioxane into a round-bottom flask, dropwise adding a sodium hydroxide solution into the mixture, stirring at room temperature, adding hydrochloric acid into the reaction system, adjusting the pH value to 1-2, and separating and purifying to obtain a compound 3;
(3) preparation of compound 4:
respectively adding a compound 3, N-methylaniline, 1-hydroxybenzotriazole, (3mmol) 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and N, N' -dimethylformamide into a round-bottom flask, stirring the mixture at room temperature, and separating and purifying to obtain a compound 4;
(4) preparation of compound 5:
respectively adding a compound 4 and 1, 3-propane diamine into a round-bottom flask, stirring the reaction system at room temperature, and separating and purifying the reaction system to obtain a compound 5;
(5) preparation of compound 6:
respectively adding a compound 5, trifluoroacetic acid and water into a round-bottom flask, stirring at room temperature, concentrating to dryness, adding salicylaldehyde and ethanol into the concentrated system, dropwise adding triethylamine, adjusting to alkalescence, stirring at room temperature for reaction, concentrating the reaction system to dryness, and separating and purifying to obtain a compound 6, wherein the compound 6 is a bilateral asymmetric substituent substituted tartaric acid skeleton compound.
4. The bilateral asymmetric substituent substituted tartaric acid framework compound according to claim 3, wherein the molar ratio between compound 1 and boron trifluoride ethyl ether in step (1) is 1: 1.2.
5. The bilateral asymmetric substituent-substituted tartaric acid framework compound of claim 3, wherein the molar ratio of compound 2 in (2) to sodium hydroxide in sodium hydroxide solution is 1: 1.04.
6. The bilateral asymmetric substituent-substituted tartaric acid framework compound of claim 3, wherein the molar ratio between compound 3 and N-methylaniline in (3) is 1: 1.5;
the molar ratio of the compound 3 to the 1-hydroxybenzotriazole in the step (3) is 1: 1.5;
the molar ratio of the compound 3 to the 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride in the (3) is 1: 1.5.
7. The bilateral asymmetric substituent substituted tartaric acid skeleton compound of claim 3, wherein the molar ratio between compound 5 and salicylaldehyde in (5) is 1: 1.2.
8. The bilateral asymmetric substituent-substituted tartaric acid framework compound of claim 3, wherein the separation and purification in steps (1) to (5) comprises column chromatography.
9. Use of a compound based on a bilaterally asymmetric substituent substituted tartaric acid backbone according to any one of claims 1-8 in the synthesis of chiral pharmaceutical intermediates.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103086859A (en) * | 2011-11-08 | 2013-05-08 | 清华大学 | 2,4-dihydroxy-5,6-substituted-1-halogenobenzene derivative, synthesis method and application thereof |
| CN103272638A (en) * | 2013-06-04 | 2013-09-04 | 大连理工大学 | Chiral guanidine catalysts based on tartaric acid skeleton, preparation method and application thereof |
| US20160145280A1 (en) * | 2013-04-19 | 2016-05-26 | Agency For Science, Technology And Research | Tunable fluorescence using cleavable linkers |
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- 2020-12-23 CN CN202011537014.9A patent/CN112645839A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103086859A (en) * | 2011-11-08 | 2013-05-08 | 清华大学 | 2,4-dihydroxy-5,6-substituted-1-halogenobenzene derivative, synthesis method and application thereof |
| US20160145280A1 (en) * | 2013-04-19 | 2016-05-26 | Agency For Science, Technology And Research | Tunable fluorescence using cleavable linkers |
| CN103272638A (en) * | 2013-06-04 | 2013-09-04 | 大连理工大学 | Chiral guanidine catalysts based on tartaric acid skeleton, preparation method and application thereof |
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