Preparation method for bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester

A technology of dimethyl dicarboxylate and pentane, applied in the preparation of carboxylic acid halides, organic chemistry, etc., can solve the problems of no suitable industrial synthesis methods, and achieve the effects of convenient operation, easy reaction, and short route

Inactive Publication Date: 2016-02-03
SHANGHAI STA PHARMA R&D CO LTD +3
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mainly solve the technical problem that there is no suitable industrial synthesis method at present

Method used

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  • Preparation method for bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester
  • Preparation method for bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester

Examples

Experimental program
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Effect test

Embodiment 1

[0010] Example 1: a. Compound 1 (100g, 0.8mol) and 18-crown-6 ether (5g) and pinacol (8g) were dissolved in bromoform (400g) and hydrogen was added dropwise at 10°C to 25°C Sodium oxide (30% by mass, 1.0 L) aqueous solution, and then the reaction system was stirred at room temperature for 24 hours. TLC (petroleum ether / ethyl acetate=10 / 1, volume ratio, the same below) showed that the reaction was complete. After the reaction system was concentrated, it was purified by chromatographic column (petroleum ether / ethyl acetate=5 / 1 to 1 / 1) to obtain the pure compound 2 (168g), with a yield of 70.7%.

[0011] δ3.301(s,4H),1.061(s,2H).

[0012] b. Compound 2 (101 g, 0.338 mol) was dissolved in tetrahydrofuran (200 mL), and methyllithium in tetrahydrofuran (1.6 M, 600 mL) was added dropwise at -30°C to -40°C. After the dropwise addition, the reaction system was slowly raised to room temperature and stirred for 2 small tests. The solution of compound 2 was obtained, which was directly...

Embodiment 2

[0020] Example 2: a. Compound 1 (500g, 4mol) and 18-crown-6 ether (25g) and pinacol (40g) were dissolved in bromoform (2kg) and added dropwise at 10°C to 25°C for oxidation Sodium (mass percent concentration 30%, 5.0L) aqueous solution. Then the reaction system was stirred at room temperature for 24 hours. TLC (petroleum ether / ethyl acetate=10 / 1) showed that the reaction was complete. After the reaction system was concentrated, it was purified by chromatographic column (petroleum ether / ethyl acetate=5 / 1 to 1 / 1) to obtain the pure compound 2 (840g), with a yield of 70.7%.

[0021] δ3.301(s,4H), 1.061(s,2H).

[0022] b. Compound 2 (505 g, 1.69 mol) was dissolved in tetrahydrofuran (800 mL), and methyllithium in tetrahydrofuran (1.6 M, 3.0 L) was added dropwise at -30°C to -40°C. After the dropwise addition, the reaction system was slowly raised to room temperature and stirred for 2 small tests. The solution of compound 2 was obtained, which was directly used in the next react...

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PUM

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Abstract

The invention relates to a preparation method for bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester, and mainly solves the technical problem that a method suitable for industrial synthesis does not exist at present. The preparation method comprises the following six steps: firstly, reacting a compound (1) and bromoform under an alkaline condition to obtain a compound (2); secondly, reacting the compound (2) and lithium methide to obtain a compound (3); thirdly, illuminating the compound (3) and diacetyl by a high-pressure mercury lamp to obtain a compound (4); fourthly, treating with sodium hypochlorite to obtain a compound (5); fifthly, reacting the compound (5) and thionyl chloride to obtain a compound (6); and finally, treating the compound (6) under the effect of methanol to obtain a compound (7) which is a final product. A reaction formula is as shown in the specification, and the acquired bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester is a useful midbody or product for synthesis of many drugs.

Description

technical field [0001] The invention relates to a synthesis method of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid dimethyl ester (CAS: 115913-32-1). Background technique [0002] Dimethyl bicyclo[1.1.1]pentane-1,3-dicarboxylate and related derivatives are widely used in medicinal chemistry and organic synthesis. At present, the synthesis of bicyclo[1.1.1]pentane-1,3-dicarboxylate dimethyl mainly takes cyclobutane derivatives as raw materials, and synthesizes bicyclo[1.1.1]pentane by alkylation reaction. The rate is low and there are great limitations in the development of derivative molecules. Therefore, it is necessary to develop a synthetic method with readily available raw materials, convenient operation, easy control of the reaction, and suitable overall yield. Contents of the invention [0003] The purpose of the present invention is to develop a synthetic method of bicyclo[1.1.1]pentane-1,3-dicarboxylate dimethyl with easy-to-obtain raw materials, convenient operat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/753C07C67/14
Inventor 万晓君毕增梁王海慧沈万军彭雁南程圆邵文庆陈玉燕袁晓斌于凌波李磊哈维杰柴艳萍周乐乐吴璇朱喜雯马坤艳陈远丽何振民马汝建陈民章傅小勇王文贵
Owner SHANGHAI STA PHARMA R&D CO LTD
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