Preparation method of substituted methylene benzocyclodecene ketoxime

A technology of benzocyclodecene and methylene, which is applied in the field of synthesis of pharmaceutical compounds, can solve the problems of cumbersome reaction process, large environmental pollution, and difficult operation, and achieve the effects of high safety, good product quality, and easy control of the process

Active Publication Date: 2010-03-17
YANGTZE RIVER PHARM GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it needs to be distilled under low temperature and high vacuum conditions. The reaction process uses flammable and explosive ether as the extraction agent. The reaction process is cumbersome, difficult to operate, unsafe, and pollutes the environment.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] 1-(5-Bromopentyl)-7-methoxy-1-methyl-tetralone (A)

[0024] Raw material ratio

[0025] raw material name

Feeding amount

molecular weight

moles

7-Methoxy-1-methyl-2-tetralone

5.47kg

190

28.8

1,5 dibromopentane

13.25kg

230

57.6

Tetrabutylammonium bromide

4.64kg

322.4

14.4

NaOH

2kg

Toluene

35.7L

[0026] Steps

[0027] Add 5.47 kg of intermediate 7-methoxy-1-methyl-2-tetralone and 35.7 L of toluene and stir to dissolve. 40% sodium hydroxide solution and 4.64 kg of tetrabutylammonium bromide were added. Cool the iced brine to -2-4°C, add 13.25 kg of 1,5-dibromopentane dropwise, and drop it in 40 minutes. The inner temperature is 20-35°C, and the reaction takes 6 hours. Pour into a separatory funnel, separate the toluene layer, add toluene to the alkaline aqueous layer to extract, and combine the toluene layers. The toluene layer wa...

Embodiment 2

[0029] 1-(5-Bromopentyl)-7-methoxy-1-methyl-tetralone (B)

[0030] Raw material ratio

[0031] raw material name

Feeding amount

molecular weight

moles

7-Methoxy-1-methyl-2-tetralone

5.47kg

190

28.8

1,5 dibromopentane

13.25kg

230

57.6

Tetrabutylammonium bromide

4.64kg

322.4

14.4

NaOH

2kg

Toluene

35.7L

[0032] Steps

[0033] Add 5.47 kg of intermediate 7-methoxy-1-methyl-2-tetralone and 35.7 L of xylene and stir to dissolve. 30% sodium hydroxide solution and 4.64 kg of tetrabutylammonium bromide were added. Cool the iced brine to -2-4°C, add 13.25 kg of 1,5-dibromopentane dropwise, and drop it in 35 minutes. The inner temperature is 20-35°C, and the reaction takes 6 hours. Pour into a separatory funnel, separate the xylene layer, add xylene to the alkaline water layer to extract, and combine the xylene layers. Wash the xylene layer with...

Embodiment 3

[0035] 1-(5-Bromopentyl)-7-methoxy-1-methyl-tetralone (C)

[0036] Raw material ratio

[0037] raw material name

Feeding amount

molecular weight

moles

7-Methoxy-1-methyl-2-tetralone

5.47kg

190

28.8

1,5 dibromopentane

13.25kg

230

57.6

Tetrabutylammonium bromide

4.64kg

322.4

14.4

[0038] NaOH

2kg

Toluene

35.7L

[0039] Steps

[0040] Add 5.47 kg of intermediate 7-methoxy-1-methyl-2-tetralone and 35.7 L of toluene and stir to dissolve. Add 50% sodium hydroxide solution and 4.64 kg of tetrabutylammonium bromide. Cool the iced brine to -2-4°C, add 13.25 kg of 1,5-dibromopentane dropwise, and drop it in 45 minutes. The inner temperature is 20-35°C, and the reaction takes 6 hours. Pour into a separatory funnel, separate the toluene layer, add toluene to the alkaline aqueous layer to extract, and combine the toluene layers. The tolu...

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PUM

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Abstract

The invention discloses a preparation method which is characterized by using 7-methoxy-1-methyl-2-tetralone as an initial raw material to synthesize 5,6,7,8,9,10,11,12-octahydro-3-methoxy-5-methyl-5,11-methylene benzocyclodecene-13-ketoxime. In the method, 1,5-dibromopentane is taken as an alkylating agent in alkaline environment in the presence of methylbenzene and other solution as well as phase transfer catalysts to carry out alkylation reaction, forms ring in the presence of sodium hydride and then reacts with hydroxylamine hydrochloride. The preparation method of the invention features mild reaction conditions, avoids the defects of low temperature required originally, requirement of high vacuum distillation, use of diethyl ether for extraction, complex operation and the like, and has the advantages of simple operation, high safety, good product quality and low cost, etc.

Description

technical field [0001] The present invention relates to the synthesis of pharmaceutical compounds, more specifically, to a 5,6,7,8,9,10,11,12-octahydro-3-methoxy-5-methyl-5,11- The preparation method of methylene benzocyclodecene-13-one oxime. Background technique [0002] Dezocine is an analgesic that acts on opioid receptors. It has both agonist and antagonist effects. The analgesic effect is equivalent to that of morphine and 5-9 times stronger than that of pethidine. It has mild side effects and is well tolerated. This product was developed by AstraZeneca, approved by the FDA in 1989, and launched in the United States in 1990. [0003] 5,6,7,8,9,10,11,12-Octahydro-3-methoxy-5-methyl-5,11-methylenebenzocyclodecen-13-one oxime, which is synthesized An important intermediate of dezocine. In U.S. Patent No. 3,836,670 disclosed by Meier in 1974, 7-methoxyl-1-methyl-2-tetralone was used as a starting material to synthesize 5,6,7,8,9,10,11,12 -Octahydro-3-methoxy-5-methyl-5...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C251/44C07C249/08
Inventor 赵文镜戚苏民孙田江储结根尹必喜张玉斌刘江华高力虎陆宏国袁会峰
Owner YANGTZE RIVER PHARM GRP CO LTD
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