2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-azaspiro(3.4)octane synthesis method

A technology of tert-butoxycarbonyl and synthesis method, which is applied in the field of synthesis of 2-tert-butoxycarbonyl-7-carbonyl-5-oxo-2-azaspiro(3.4) octane, which can solve the problem of expensive reagents and expensive , high risk and other problems, to achieve the effect of reasonable reaction process design, saving synthesis cost, and short synthesis route

Inactive Publication Date: 2015-11-04
SHANGHAI SYNTHEALL PHARM CO LTD +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

For this intermediate, although the literature has been reported, its route is as follows, wherein the synthetic compound 2 needs to use highly explosive hydrogen peroxide and expensive catalyst methyltrioxyrhenium, and the catalyst...

Method used

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  • 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-azaspiro(3.4)octane synthesis method
  • 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-azaspiro(3.4)octane synthesis method
  • 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-azaspiro(3.4)octane synthesis method

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Experimental program
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Embodiment 1

[0015]

[0016] Slowly add 130 grams of sodium bisulfite aqueous solution to 120 grams of compound 2 and 130 g of sodium periodate in 2.8 liters of acetonitrile aqueous solution (volume ratio, 3:1), and the reaction solution was slowly raised to 25° C. to react overnight. compound 2 If the reaction is not complete, add saturated sodium thiosulfate solution to quench the reaction, extract with ethyl acetate, wash the organic layer with water and add anhydrous sodium sulfate to dry, filter, and rotary evaporate under reduced pressure to obtain a yellow oil, and obtain a crude product, column chromatography Isolation and Purification. Yield: 20%.

[0017] 1 H-NMR (CDCl3): 4.10-3.90 (m, 6H), 3.60 (m, 1H), 5.19-5.18 (m, 1H), 2.10-1.81 (m, 2H), 1.43 (s, 9H).

Embodiment 2

[0019]

[0020] Slowly add 130 grams of sodium bisulfite aqueous solution to 120 grams of compound 2 and 130 grams of sodium periodate in 2.8 liters of acetonitrile aqueous solution (volume ratio, 3:1), and the reaction solution was slowly raised to 50° C. to react overnight. After the reaction was completed, saturated sodium thiosulfate solution was added to quench the reaction, extracted with ethyl acetate, the organic layer was washed with water and dried by adding anhydrous sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a yellow oil, and the crude product was separated by column chromatography. purification. Yield: 42%.

Embodiment 3

[0022]

[0023] Slowly add 130 grams of sodium bisulfite aqueous solution to 120 grams of compound 2 and 130 g of sodium periodate in 2.8 liters of acetonitrile aqueous solution (volume ratio, 3:1), and the reaction solution was slowly raised to 80° C. to react overnight. After the reaction was completed, saturated sodium thiosulfate solution was added to quench the reaction, extracted with ethyl acetate, the organic layer was washed with water and dried by adding anhydrous sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a yellow oil, and the crude product was separated by column chromatography. purification. Yield: 60%.

[0024] Synthesis of tert-butoxycarbonyl-7-carbonyl-5-oxo-2-azaspiro(3.4)octane

[0025] Example 1

[0026]

[0027] 44 g compound 3 It was dissolved in 400 ml of dichloromethane solution, slowly added dropwise to a mixture of 50 g of manganese dioxide and 400 ml of dichloromethane under ice-cooling, and then...

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Abstract

The present invention relates to a 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-spiro(3.4)octane synthesis method. A purpose of the present invention is mainly to solve the technical problems of high price of the reagent used in the existing synthesis route, high risk and no suitability for industrial production. According to the present invention, the three-step method is used to synthesize, wherein the first step is that a saturated ammonium chloride aqueous solution of zinc powder is added to a tetrahydrofuran solution of 1-tertbutyloxycarbonyl-3-azetidinone, then allyl bromide is added in a dropwise manner, and the reaction solution reacts at a room temperature overnight to obtain 1-tertbutyloxycarbonyl-3-allyl-azetidinol, the step is that an aqueous solution of sodium hydrogen sulfite is added to an acetonitrile aqueous solution of the 1-tertbutyloxycarbonyl-3-allyl-azetidinol and sodium periodate, and stirring is performed for 16 h at a temperature of 80 DEG C to obtain 2-tertbutyloxycarbonyl-7-hydroxy-5-O-2-azaspiro(3.4)octane, and the third step is that pyridinium chlorochromate is added to a dichloromethane solution of the 2-tertbutyloxycarbonyl-7-hydroxy-5-O-2-azaspiro(3.4)octane under ice bath, and a reaction is performed at a room temperature overnight to obtain the 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-spiro(3.4)octane.

Description

technical field [0001] The invention relates to a practical synthesis method of 2-tert-butoxycarbonyl-7-carbonyl-5-oxo-2-azaspiro(3.4)octane. Background technique [0002] 2-tert-butoxycarbonyl-7-carbonyl-5-oxo-2-azaspiro(3.4)octane is an existing commonly used intermediate in organic synthesis (CAS: 1408075-90-0), which can be aminated by reductive amination , can be converted from ketones to primary amines, and the market sales are very good. For this intermediate, although the literature has been reported, its route is as follows, wherein the synthetic compound 2 needs to use highly explosive hydrogen peroxide and expensive catalyst methyltrioxyrhenium, and the catalyst used for the synthetic compound 3 is bis(trifluoro Methylsulfonyl) amido triphenylphosphine is also expensive, and the reagents used in this synthetic route are expensive and dangerous, and are not suitable for industrial production. And the present invention uses the same starting material to develop a ...

Claims

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Application Information

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IPC IPC(8): C07D491/107
CPCC07D491/107
Inventor 刘月领徐学芹周强安自强白雪刘璇何燕平于华夏章洋毛延军于凌波何振民马汝建
Owner SHANGHAI SYNTHEALL PHARM CO LTD
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