CN115850157A - Preparation method of 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate - Google Patents
Preparation method of 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate Download PDFInfo
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- -1 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate Chemical compound 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 17
- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 claims abstract description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- MSHSHVZVLWLNIO-UHFFFAOYSA-N (1-benzylpiperidin-4-yl) n-(2-phenylphenyl)carbamate Chemical compound C1CN(CC=2C=CC=CC=2)CCC1OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 MSHSHVZVLWLNIO-UHFFFAOYSA-N 0.000 claims description 11
- BPPZXJZYCOETDA-UHFFFAOYSA-N 1-benzylpiperidin-4-ol Chemical compound C1CC(O)CCN1CC1=CC=CC=C1 BPPZXJZYCOETDA-UHFFFAOYSA-N 0.000 claims description 11
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000008096 xylene Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- LXZYLGUNAYNUGX-UHFFFAOYSA-N methyl n-(2-phenylphenyl)carbamate Chemical class COC(=O)NC1=CC=CC=C1C1=CC=CC=C1 LXZYLGUNAYNUGX-UHFFFAOYSA-N 0.000 claims description 2
- 238000007789 sealing Methods 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 1
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 238000005886 esterification reaction Methods 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 230000006837 decompression Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 6
- IHHUGFJSEJSCGE-UHFFFAOYSA-N 1-isocyanato-2-phenylbenzene Chemical compound O=C=NC1=CC=CC=C1C1=CC=CC=C1 IHHUGFJSEJSCGE-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
Abstract
The invention discloses a preparation method of 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate, belonging to the field of synthesis of drug intermediates. The method takes 2-aminobiphenyl as a raw material to synthesize 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate through esterification reaction and substitution reaction. The invention provides a preparation method of 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate, which has the advantages of controllable reaction process, simple operation, high yield and good product purity.
Description
Technical Field
The invention belongs to the field of synthesis of pharmaceutical intermediates, and relates to a preparation method of 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate.
Background
1-Benzylpiperidin-4-yl [1,1' -biphenyl]-2-ylcarbamate of formula: c 25 H 26 N 2 O 2 Molecular weight: 386.49, CAS:171723-80-1, the chemical formula is as follows:
the 1-benzylpiperidin-4-yl [1,1 '-biphenyl ] -2-ylcarbamate is a key intermediate for synthesizing Lei Fen nancine, and the current synthetic route mainly comprises two routes, wherein the first route (CN 106632257) is to synthesize the 1-benzylpiperidin-4-yl [1,1' -biphenyl ] -2-ylcarbamate by using 2-aminobiphenyl and 1- (phenylmethyl) -4-piperidinyl-1H-imidazole-1-carboxylic acid ester as raw materials, and the specific synthetic route is as follows:
the route takes 2-aminobiphenyl and 1- (phenylmethyl) -4-piperidyl-1H-imidazole-1-carboxylic ester as raw materials to synthesize 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-ylcarbamate through 1-step reaction, the reaction temperature reaches-50 ℃ at the lowest, the overall yield is low, nitrogen protection is used, the reaction steps are increased, and the overall yield is reduced.
Patent WO9964043 reports a process for synthesizing 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate by using 2-biphenylyl isocyanate as a raw material and adding N-benzyl-4-piperidinol through a one-step method, wherein the specific synthetic route is as follows:
the price of the route is high, 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate is synthesized by a one-step method, and 2-biphenyl isocyanate is expensive and unstable, so that the generation cost is high and the purification is difficult.
Disclosure of Invention
The invention provides a preparation method of 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate aiming at the defects in the prior art.
The method comprises the following steps of taking 2-aminobiphenyl and methyl chloroformate as raw materials, and carrying out ice-water bath reaction for 2 hours in tetrahydrofuran and alkali to obtain methyl [1,1' -biphenyl ] -2-yl carbamate; methyl [1,1 '-biphenyl ] -2-yl carbamate is added into a solvent, 1-benzyl-4-hydroxypiperidine is added dropwise, and the reaction is carried out at a certain temperature to generate 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate, wherein the specific synthetic route is as follows:
s1, adding 2-aminobiphenyl and alkali into a solvent, reducing the temperature of a reaction solution to a certain temperature under the protection of nitrogen, dropwise adding methyl chloroformate, heating to room temperature for continuous reaction, and treating the mixture with 1M HCl aqueous solution after the reaction is finished. Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 Washing with saline, drying and concentrating to obtain methyl [1,1' -biphenyl]-2-ylcarbamates;
s2, adding N-benzyl-4-hydroxypiperidine and methyl [1,1 '-biphenyl ] -2-yl carbamate into a high-pressure reaction kettle, adding a solvent, sealing, and heating to a certain temperature to generate 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate.
The solvent in the step S1 is one or more of tetrahydrofuran, 1,2-dichloroethane, dichloromethane, acetonitrile and N, N-dimethylformamide, and is preferably dichloromethane; the reaction temperature was 3 ℃. The alkali is one or more of pyridine, triethylamine, 4-dimethylamino pyridine and N, N-diisopropylethylamine, and is preferably pyridine;
the reaction temperature in the step S2 is 110 ℃; the pressure resistance value of the high-pressure reaction kettle is more than or equal to 5 MPa; the reaction solvent is one or more of toluene, xylene and chlorobenzene, and is preferably xylene.
The invention has the beneficial effects that:
(1) Methyl chloroformate is selected as an acylation reagent, so that the method has high reaction activity, good selectivity and low cost.
(2) The reaction route is short, and the 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate can be synthesized by only 2 steps of reaction; the product has good purity and high yield, the total yield of the two-step reaction is 87%, and the product purity is more than 99%.
Detailed Description
Example 1:
adding dichloromethane (300 mL), 2-aminobiphenyl (50 g) and pyridine (25.7 g) into a 500 mL three-neck flask, reducing the temperature to 3 ℃ under the protection of nitrogen, dropwise adding methyl chloroformate (30.7 g), enabling the temperature of a system in the dropwise adding process not to exceed 5 ℃, raising the temperature to room temperature after the dropwise adding is finished, and reacting 1 h. The mixture was treated with 1M aqueous HCl (50 mL). Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to give an oily liquid.
The oily matter, 1-benzyl-4-hydroxypiperidine (56.5 g) and xylene (300 mL) are added into a high-pressure reaction kettle of 500 mL to react at 110 ℃ for 5 h, the mixture is cooled to room temperature of 20-25 ℃, the solvent is removed by decompression and concentration to obtain a white solid crude product, and the white solid crude product is recrystallized by methanol to obtain a white solid, wherein the yield of the two steps is 85 percent, and the purity is 99 percent.
Example 2:
1,2-dichloroethane (300 mL), 2-aminobiphenyl (50 g) and pyridine (25.7 g) are added into a 500 mL three-neck flask, the temperature is reduced to 3 ℃, methyl chloroformate (30.7 g) is dripped, the temperature of the dripping process system does not exceed 5 ℃, the temperature is raised to the room temperature after the dripping is finished, and 1h is reacted. The mixture was treated with 1M aqueous HCl (50 mL). Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 (50 mL) and brine (50 mL) and dried over anhydrous sodium sulfate and concentrated to give an oily liquid.
The oily substance, 1-benzyl-4-hydroxypiperidine (56.5 g) and xylene (300 mL) are added into a high-pressure reaction kettle of 500 mL to react at 110 ℃ for 5 h, the mixture is cooled to room temperature of 20-25 ℃, the solvent is removed by decompression and concentration to obtain a crude white solid, and the crude white solid is recrystallized by methanol to obtain a white solid, wherein the yield of the two steps is 84% and the purity of the two steps is 99%.
Example 3:
adding dichloromethane (300 mL), 2-aminobiphenyl (50 g) and triethylamine (32.9 g) into a 500 mL three-neck flask, reducing the temperature to 3 ℃ under the protection of nitrogen, dropwise adding methyl chloroformate (30.7 g), keeping the temperature of the system not exceeding 5 ℃ in the dropwise adding process, raising the temperature to room temperature after the dropwise adding is finished, and reacting 1 h. With 1M HCl(50 mL) the mixture is treated with an aqueous solution. Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 (50 mL) and brine (50 mL) and dried over anhydrous sodium sulfate and concentrated to give an oily liquid.
The oily substance, 1-benzyl-4-hydroxypiperidine (56.5 g) and toluene (300 mL) are added into a high-pressure reaction kettle of 500 mL to react at 110 ℃ for 5 h, the mixture is cooled to room temperature of 20-25 ℃, the solvent is removed by decompression and concentration to obtain a crude white solid, and the crude white solid is recrystallized by methanol to obtain a white solid, wherein the yield of the two steps is 82 percent, and the purity of the two steps is 99 percent.
Example 4:
tetrahydrofuran (300 mL), 2-aminobiphenyl (50 g) and pyridine (25.7 g) are added into a 500 mL three-neck flask, the temperature is reduced to 3 ℃ under the protection of nitrogen, methyl chloroformate (30.7 g) is dripped, the temperature of the system in the dripping process does not exceed 5 ℃, the temperature is raised to the room temperature after the dripping is finished, and 1h is reacted. The mixture was treated with 1M aqueous HCl (50 mL). Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 (50 mL) and brine (50 mL) and dried over anhydrous sodium sulfate and concentrated to give an oily liquid.
The oily substance, 1-benzyl-4-hydroxypiperidine (56.5 g) and xylene (300 mL) are added into a high-pressure reaction kettle of 500 mL to react at 110 ℃ for 5 h, the mixture is cooled to room temperature of 20-25 ℃, and the solvent is removed by decompression and concentration to obtain a white solid crude product, and the white solid crude product is recrystallized by methanol to obtain a white solid, wherein the yield of the two steps is 84% and the purity of the white solid is 99%. Example 5:
adding N, N-dimethylformamide (300 mL), 2-aminobiphenyl (50 g) and pyridine (25.7 g) into a 500 mL three-neck flask, cooling to 3 ℃, dropwise adding methyl chloroformate (30.7 g), wherein the temperature of the system in the dropwise adding process is not more than 5 ℃, heating to room temperature after the dropwise adding is finished, and reacting for 1 h. The mixture was treated with 1M aqueous HCl (50 mL). Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 (50 mL) and brine (50 mL) and dried over anhydrous sodium sulfate and concentrated to give an oily liquid.
The oily substance, 1-benzyl-4-hydroxypiperidine (56.5 g) and toluene (300 mL) are added into a high-pressure reaction kettle of 500 mL to react at 110 ℃ for 5 h, the mixture is cooled to room temperature of 20-25 ℃, the solvent is removed by decompression and concentration to obtain a crude white solid, and the crude white solid is recrystallized by methanol to obtain a white solid, wherein the yield of the two steps is 84% and the purity of the two steps is 99%.
Example 6:
adding acetonitrile (300 mL), 2-aminobiphenyl (50 g) and pyridine (25.7 g) into a 500 mL three-neck flask, reducing the temperature to 3 ℃ under the protection of nitrogen, dropwise adding methyl chloroformate (30.7 g), enabling the temperature of a system in the dropwise adding process not to exceed 5 ℃, raising the temperature to room temperature after the dropwise adding is finished, and reacting 1 h. The mixture was treated with 1M aqueous HCl (50 mL). Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 (50 mL) and brine (50 mL) and dried over anhydrous sodium sulfate and concentrated to give an oily liquid.
The oily substance, 1-benzyl-4-hydroxypiperidine (56.5 g) and chlorobenzene (300 mL) are added into a high-pressure reaction kettle of 500 mL to react at 110 ℃ for 5 h, the mixture is cooled to room temperature of 20-25 ℃, and the solvent is removed by decompression and concentration to obtain a white solid crude product, and the white solid crude product is recrystallized by methanol to obtain a white solid, wherein the yield of the two steps is 84% and the purity of the white solid is 99%.
Comparative example:
methylene chloride (300 mL), 2-aminobiphenyl (50 g), triphosgene (43.8 g) and pyridine (25.7 g) were added to a 500 mL three-necked flask, and the mixture was cooled to 3 ℃ under nitrogen protection and reacted for 30min. Warmed to room temperature and reacted 1 h. The mixture was treated with 1M aqueous HCl (50 mL). Extracting with ethyl acetate, and sequentially extracting with 1M NaCO 3 (50 mL) and brine (50 mL) and dried over anhydrous sodium sulfate and concentrated to give an oily liquid.
The oily substance, 1-benzyl-4-hydroxypiperidine (56.5 g) and toluene (300 mL) are added into a high-pressure reaction kettle of 500 mL to react at 80 ℃ for 5 h, the mixture is cooled to room temperature of 20-25 ℃, the solvent is removed by decompression and concentration to obtain a crude white solid, and the crude white solid is recrystallized by methanol to obtain a white solid, wherein the yield of the two steps is 70 percent, and the purity of the two steps is 96 percent.
Although the present invention has been described with reference to the specific embodiments, it should be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.
Claims (7)
1. A preparation method of 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate is characterized in that the synthetic route of the preparation method is as follows:
s1: adding 2-aminobiphenyl and alkali into a solvent, reducing the temperature of reaction liquid to a certain temperature under the protection of nitrogen, dropwise adding methyl chloroformate, heating to room temperature for continuous reaction, treating the mixture with 1M HCl aqueous solution after the reaction is finished, extracting with ethyl acetate, and sequentially using 1M NaCO 3 Washing with saline, drying and concentrating to obtain methyl [1,1' -biphenyl]-2-ylcarbamates;
s2: adding N-benzyl-4-hydroxypiperidine and methyl [1,1 '-biphenyl ] -2-yl carbamate into a high-pressure reaction kettle, adding a solvent, sealing, and heating to a certain temperature to generate 1-benzyl piperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate.
2. The method for preparing 1-benzylpiperidin-4-yl [1,1' -biphenyl ] -2-ylcarbamate according to claim 1, wherein the solvent in the step S1 is one or more of tetrahydrofuran, 1,2-dichloroethane, dichloromethane, acetonitrile, N-dimethylformamide.
3. The process for preparing 1-benzylpiperidin-4-yl [1,1' -biphenyl ] -2-ylcarbamate according to claim 1, wherein the reaction temperature in the step S1 is 3 ℃.
4. The method for preparing 1-benzylpiperidin-4-yl [1,1' -biphenyl ] -2-ylcarbamate according to claim 1, wherein the base in the step S1 is one or more of triethylamine, pyridine, 4-dimethylaminopyridine and N, N-diisopropylethylamine.
5. The method for preparing 1-benzylpiperidin-4-yl [1,1' -biphenyl ] -2-ylcarbamate according to claim 1, wherein the reaction temperature in the S2 step is 110 ℃.
6. The method for preparing 1-benzylpiperidin-4-yl [1,1' -biphenyl ] -2-ylcarbamate according to claim 1, wherein the pressure-resistant value of the autoclave in the step S2 is not less than 5 MPa.
7. The method for preparing 1-benzylpiperidin-4-yl [1,1' -biphenyl ] -2-ylcarbamate according to claim 1, wherein the reaction solvent in the S2 step is one or more of toluene, xylene, and chlorobenzene.
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| CN202211518287.8A CN115850157A (en) | 2022-11-30 | 2022-11-30 | Preparation method of 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate |
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| CN202211518287.8A CN115850157A (en) | 2022-11-30 | 2022-11-30 | Preparation method of 1-benzylpiperidine-4-yl [1,1' -biphenyl ] -2-yl carbamate |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0747355A1 (en) * | 1994-02-10 | 1996-12-11 | Yamanouchi Pharmaceutical Co. Ltd. | Novel carbamate derivative and medicinal composition containing the same |
| CN1140447A (en) * | 1994-02-10 | 1997-01-15 | 山之内制药株式会社 | Novel carbamate deriv. and medicinal composition contg. the same |
| JP2011111433A (en) * | 2009-11-30 | 2011-06-09 | Taiho Yakuhin Kogyo Kk | Uracil compound having ureide structure or salt thereof |
| CN106632257A (en) * | 2016-12-15 | 2017-05-10 | 上海市奉贤区中心医院 | Synthetic method of GSK961081 and intermediate thereof |
| CN115403509A (en) * | 2021-05-27 | 2022-11-29 | 山东新时代药业有限公司 | Preparation method of lefenacin intermediate |
-
2022
- 2022-11-30 CN CN202211518287.8A patent/CN115850157A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0747355A1 (en) * | 1994-02-10 | 1996-12-11 | Yamanouchi Pharmaceutical Co. Ltd. | Novel carbamate derivative and medicinal composition containing the same |
| CN1140447A (en) * | 1994-02-10 | 1997-01-15 | 山之内制药株式会社 | Novel carbamate deriv. and medicinal composition contg. the same |
| JP2011111433A (en) * | 2009-11-30 | 2011-06-09 | Taiho Yakuhin Kogyo Kk | Uracil compound having ureide structure or salt thereof |
| CN106632257A (en) * | 2016-12-15 | 2017-05-10 | 上海市奉贤区中心医院 | Synthetic method of GSK961081 and intermediate thereof |
| CN115403509A (en) * | 2021-05-27 | 2022-11-29 | 山东新时代药业有限公司 | Preparation method of lefenacin intermediate |
Non-Patent Citations (1)
| Title |
|---|
| TAKUYA NAMBA: "Atropisomeric Properties of N‑Acyl/N‑Sulfonyl 5H‑Dibenzo[b, d]azepin-7(6H)‑ones", 《J. ORG. CHEM.》, vol. 86, pages 7563 * |
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