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Method and device for ring-opening and fluorination reactions of steroidal epoxy compounds

A technology of epoxy compound and fluorination reaction, which is applied in the field of ring-opening of steroidal epoxy compound, fluorination reaction, and preparation of pharmaceutical intermediates. It can solve the problems of unknown purity and achieve the goal of reducing the amount of waste water and increasing the application value. Effect

Active Publication Date: 2019-01-18
AURISCO PHARMACEUTICAL CO LTD +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] The journal "Zhongnan Pharmacy" 2014,12(9), 888-889 reported the synthesis method of steroidal acetate: under low temperature, hydrogen fluoride aqueous solution reacted with steroidal epoxy Ic, hydrogen fluoride was greatly excessive, and the crude yield of IIc was 97.5%. purity unknown

Method used

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  • Method and device for ring-opening and fluorination reactions of steroidal epoxy compounds
  • Method and device for ring-opening and fluorination reactions of steroidal epoxy compounds
  • Method and device for ring-opening and fluorination reactions of steroidal epoxy compounds

Examples

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Embodiment 1

[0038] Example 1 Steroidal epoxy compound Ia (6α-fluoro-1,4-tetraenpregna-9β,11β-epoxy-17α-hydroxyl-3,20-dione) was prepared by ring-opening and fluorination reaction to prepare 9α - Process and device for fluoro-11β-hydroxy steroid compound IIa (6α,9α-difluoro-1,4-tetraenpregna-11β,17α-dihydroxy-3,20-dione).

[0039] When the reaction device of the present invention is used, as figure 1 As shown, with the flow rate of 100g / min, the suspension (its composition weight ratio is: compound 1 / toluene / water=1 / 5 / 0.2) of the flow state that will mix uniformly is punched into from a place by feeding pump 2 In the circulation system composed of 1-3-4-5-9-1, the flow rate at the control circulation pump 1 is 20 times of the flow rate at the feeding pump 2, and the circulation liquid flowing through the circulation pump 1 and the feed liquid added at a After mixing, it is fully mixed through the high-shear reactor 3 (2900rpm high-shear centrifugal pump); in addition, HF gas is introduced...

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Abstract

The invention discloses a method of preparing a compound II, which is as shown as the following reaction formula as shown in the specification. A 9 alpha-fluorine-11 beta -hydroxyl steroidal compound II is prepared via epoxy compound ring opening and fluoridation of a steroidal epoxy compound I by taking hydrogen fluoride as a fluorination reagent in a solvent consisting of arene and water. In the formula, R is CH3, CH2OH or CH2OAc; R1 is OH; R2 is alpha-CH3 or beta-CH3; and R3 is F or H. A continuous reaction device as shown in Figure 1 can be used in the method.

Description

technical field [0001] The invention relates to medicinal chemistry, in particular to the preparation of pharmaceutical intermediates, in particular to a method and device for ring-opening and fluorination reactions of steroidal epoxy compounds. Background technique [0002] Steroidal epoxy compound, general structural formula (I), general structural formula (II) of the product 9α-fluoro-11β-hydroxy steroid after ring opening and fluorination, many halogen-containing steroidal compounds are widely used clinically. At present, in the reaction of ring-opening fluorination of epoxy compounds to obtain organic fluorides, hydrogen fluoride is basically used as the fluorination reagent. Most of the improved fluorinating reagents combined hydrogen fluoride with different electron donors to form stable complexes. The earliest discovery was "Olah reagent", that is, polyhydrofluoric acid pyridinium salt Py·9HF. The complex contains 70% HF. In addition, commonly used complexes includ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J5/00C07J7/00
CPCC07J5/0076C07J7/0055
Inventor 李景华褚定军
Owner AURISCO PHARMACEUTICAL CO LTD