Synthetic method for chiral epoxy compound of anti-HIV drug intermediate

A technology of epoxy compound and synthesis method, applied in the direction of organic chemistry and the like, can solve the problems of complex process and high cost, and achieve the effects of simple and easy synthesis method, reduced synthesis cost and high yield

Inactive Publication Date: 2016-04-06
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the existing synthetic methods are difficult

Method used

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  • Synthetic method for chiral epoxy compound of anti-HIV drug intermediate
  • Synthetic method for chiral epoxy compound of anti-HIV drug intermediate
  • Synthetic method for chiral epoxy compound of anti-HIV drug intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Embodiment 1: Preparation of BOC-L-phenylalanine (compound of formula III)

[0023]

[0024] Add 1060mL of water into a 3L three-necked flask, add 106g of NaOH solid under ice bath, and stir until the temperature Tmax=52°C. When the temperature drops below 30°C, add 198.4g of L-phenylalanine (compound of formula II), Add THF1056mL, when T=22℃, add BoC dropwise 2 O289g, titrated for 22 minutes, at this time, the internal temperature was 37°C, reacted overnight at room temperature, and the system produced a large amount of white solid;

[0025] TLC was sampled the next day, the raw materials had been reacted, THF was removed under reduced pressure (45° C.), and the remaining aqueous phase was milky white. HCL was added thereto to adjust the pH=1, and CH 2 CL 2 (1+1) extraction twice, no product in the TLC aqueous phase, the organic phase was washed once with 500 mL of brine, and dried over sodium sulfate. The organic phase was spin-dried to obtain 332 g of an oily l...

Embodiment 2

[0026] Embodiment 2: prepare the chloroketone compound (a kind of formula VI compound) of Boc-L-phenylalanine

[0027]

[0028] Add 66.3 g of the compound of formula III and 500 mL of THF into a 1 L three-necked flask, cool down to -25° C., dropwise add 29.15 g of the compound of formula IV into the three-necked flask, and stir for 30 minutes. 27.18 g of the compound of formula V was added dropwise, reacted for 92 minutes, and kept at -25 to -28°C. A large amount of white solids were produced during the dropwise addition. Quickly filter at -5°C, wash the filter cake twice with THF (50+50) mL, transfer the filtrate to a 2L three-neck flask, cool down at about 0°C, replace with nitrogen three times, and add CH to the system dropwise 3 N 2 370mL, reacted for 90 minutes, the temperature was maintained at about 0°C, the system changed from colorless to yellow-green, and 400mL of HCl was added to the system to react overnight (room temperature);

[0029] The next day, separate ...

Embodiment 3

[0031] Embodiment 3: prepare the chloroketone compound (a kind of formula VI compound) of Boc-L-phenylalanine

[0032]

[0033] Add 70.4g of compound of formula III and 530mL of THF into a 1L three-necked flask, cool down to below -28°C, add 30g of compound of formula IV dropwise into the three-necked flask, stir for 30 minutes after dropping, add 27.5g of compound of formula V dropwise, and react for 85 minutes. Heat the system from -28°C to -30°C to produce a large amount of white solids, quickly filter at -5°C, transfer the filtrate to a 2L three-necked flask, protect the system with nitrogen, and add CH to the system dropwise 3 N 2 400mL, react for 50 minutes, maintain the temperature at around 0°C, the system turns yellow, add 700mL of HCl dropwise to the system after 1 hour, and react overnight at room temperature;

[0034] Separate the liquid the next day, collect the organic phase, use MTBE (200+200) mL for the aqueous phase until there is no product on the TLC of ...

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Abstract

The invention belongs to the field of chemical synthesis and particularly relates to a preparation method for a chiral epoxy compound of an anti-HIV drug intermediate. The method provided by the invention synthesizes the chiral epoxy compound by using a special ligand according to a route represented by the formula. L-phenylalanine used for synthesizing the anti-HIV drug intermediate is low in price and is easily available. The synthetic method is simple and feasible, the yield of the chiral epoxy compound is high, and the synthetic cost of the chiral epoxy compound is obviously lowered compared with that in an existing process.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a preparation method of a chiral epoxy compound as an anti-HIV drug intermediate. Background technique [0002] It has been reported that since the discovery of human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS), more and more related research has focused on antiviral therapy. Therefore, the demand for antiviral drugs has increased significantly, and the synthesis of chiral epoxy compounds has also attracted the attention of those skilled in the art. It is known that chiral epoxy compounds are playing an increasingly important role in the fields of modern organic synthesis and chiral drug synthesis. A number of chiral compounds with physiological activity can be synthesized through the completion of many chemical transformations of epoxy compounds. [0003] Current related researches include: "Organic Process & Development ...

Claims

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Application Information

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IPC IPC(8): C07D301/26C07D303/36
Inventor 雷新胜刘丛从
Owner FUDAN UNIV
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