Synthesis method of octahydro-4A,8-epoxy pyrido [4,3-C]azepine-6(5H)-tert-butyl formate

Abstract

The invention discloses a synthesis method of octahydro-4A,8-epoxy pyrido[4,3-C]azepine-6(5H)-tert-butyl formate. The synthesis method comprises the following steps: 1, reacting a compound 1 with a catalytic amount of osmium tetroxide and a first oxidant to obtain a compound 2; 2, oxidizing an alcoholic hydroxyl group into an aldehyde group by the compound 2 under the action of a second oxidant to obtain a compound 3; 3, subjecting the compound 3 and benzyl amine to reduction ammoniation in an inert atmosphere under the action of a first reducing agent to obtain a compound 4; 4, subjecting the compound 4 to catalytic hydrogenation through a palladium catalyst in the presence of Boc2O to obtain a compound 5; 5, reducing the compound 5 through a second reducing agent to obtain a compound 6; and 6, carrying out catalytic hydrogenation on the compound 6 under the action of a palladium catalyst to obtain a compound 7. The method disclosed by the invention has the advantages of easily available raw materials, convenience in operation, safety in reaction, suitability for amplification, short route, high total yield, suitability for industrial production and the like.

Description

Technical field

[0001] The present invention relates to the field of chemical synthesis, and more particularly to a synthesis method of octal hydrogen-4a, 8-epoxypyridine and [4,3-C] nitrogen-6 (5H)-formic acid tert-butyl ester. Background technique

[0002] Compound octahydro-4a, 8-epoxypyridine and [4,3-C] Nazo-6 (5H) -Camhalic acid tert-butyl ester (CAS: 1251010-89-5) and related derivatives in pharmaceutical chemistry And extensive use in organic synthesis. Currently, octahydro-4a, 8-epoxypyridine and [4,3-C] Nazo - 6 (5H) - Synthesis of tert-butyl formate is reported.

[0003] Therefore, it is necessary to develop a raw material easy, easy to operate, easy to control, overall yield, suitable for industrial production. Inventive content

[0004] The technical problem to be solved by the present invention is to provide a method of synthesizing octahydro-4a, 8-cycloptidine and [4,3-C] azagazo-6 (5H) -tutyl ester, which has The raw materials are easy, easy to operate, safe, eas...

Examples

Embodiment 1

[0066]

[0067] The first step: The catalytic amount of tetraced oxide was added to the compound 1 (24.6 g, 86 mmol) and NMO (15 g, 129 mmol) acetone (500 mL) solution, and the mixture was stirred at room temperature for 4 HRs. TLC (ethyl acetate) was monitored, and water (500 mL) was added to the reaction system, extracted with ethyl acetate (500 ml x 3), combined with an organic phase, dried over anhydrous sodium sulfate, filtered, filtrate to obtain Compound 2 (27 g, 84.6 mmol) is used directly for the next step.

[0068] Step 2: Compound 2 (27 g, 84.6 mmol) was dissolved in methanol (450 mL) and water (50 mL) mixed solvent at room temperature, and sodium metatanate (27 g, 127 mmol) was added, and stirred at room temperature for 4 HRs. TLC (ethyl acetate) monitoring has been completed. Water (500 mL) was added, extracted with dichloromethane (500 ml x 3), combined with an organic phase, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain...

Technical field

[0001] The present invention relates to the field of chemical synthesis, and more particularly to a synthesis method of octal hydrogen-4a, 8-epoxypyridine and [4,3-C] nitrogen-6 (5H)-formic acid tert-butyl ester. Background technique

[0002] Compound octahydro-4a, 8-epoxypyridine and [4,3-C] Nazo-6 (5H) -Camhalic acid tert-butyl ester (CAS: 1251010-89-5) and related derivatives in pharmaceutical chemistry And extensive use in organic synthesis. Currently, octahydro-4a, 8-epoxypyridine and [4,3-C] Nazo - 6 (5H) - Synthesis of tert-butyl formate is reported.

[0003] Therefore, it is necessary to develop a raw material easy, easy to operate, easy to control, overall yield, suitable for industrial production. Inventive content

[0004] The technical problem to be solved by the present invention is to provide a method of synthesizing octahydro-4a, 8-cycloptidine and [4,3-C] azagazo-6 (5H) -tutyl ester, which has The raw materials are easy, easy to operate, safe, eas...

Examples

Embodiment 1

[0066]

[0067] The first step: The catalytic amount of tetraced oxide was added to the compound 1 (24.6 g, 86 mmol) and NMO (15 g, 129 mmol) acetone (500 mL) solution, and the mixture was stirred at room temperature for 4 HRs. TLC (ethyl acetate) was monitored, and water (500 mL) was added to the reaction system, extracted with ethyl acetate (500 ml x 3), combined with an organic phase, dried over anhydrous sodium sulfate, filtered, filtrate to obtain Compound 2 (27 g, 84.6 mmol) is used directly for the next step.

[0068] Step 2: Compound 2 (27 g, 84.6 mmol) was dissolved in methanol (450 mL) and water (50 mL) mixed solvent at room temperature, and sodium metatanate (27 g, 127 mmol) was added, and stirred at room temperature for 4 HRs. TLC (ethyl acetate) monitoring has been completed. Water (500 mL) was added, extracted with dichloromethane (500 ml x 3), combined with an organic phase, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain...

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