Unlock instant, AI-driven research and patent intelligence for your innovation.

Recycling method of ketotifen intermediate mother liquid

A recovery method and a benzo-based technology, applied in the field of chemical pharmacy, can solve the problems of recovering compounds, low atomic utilization rate, undisclosed and other problems, and achieve the effects of reducing production cost and easy control of reaction process.

Active Publication Date: 2019-02-01
LINHAI HUANAN CHEM CO LTD +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Document Collect Czech Chem Commun, 1989,54,2443-2469 discloses that according to document HelveticaChimica Acta, 1976,59 (3), the synthetic method of P866-877 obtains 10-methoxy-4H-benzo[4,5]cycloheptane Triene[1,2-b]thiophen-4-one, in addition to the target product in the mother liquor, there are also a large amount of impurity A, impurity B, impurity C, and impurity D. The impurities produced cannot be reused, and the impurities produced Compound I cannot be recovered by purification method in the mother liquor, resulting in low utilization rate of atoms and generation of a large amount of three wastes
However, the prior art has not disclosed the recovery method of the mother liquor, so a method containing 10-methoxy-4H-benzo[4,5]cycloheptatrienyl[1,2-b]thiophen-4-one was developed. The recycling method is of great significance

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Recycling method of ketotifen intermediate mother liquid
  • Recycling method of ketotifen intermediate mother liquid
  • Recycling method of ketotifen intermediate mother liquid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] According to the document Helvetica Chimica Acta, 1976, 59 (3), P866-877, the preparation method described in the preparation of 10-methoxy-4H-benzo [4,5] cycloheptatriene [1,2-b] thiophene -4-ketone, as follows:

[0034] Add 120.0g of dibromide (compound II) and 1200mL of methanol into the reaction flask, heat up to reflux, react for 7 hours, then add 44.0g of potassium hydroxide, continue to reflux for 7 hours, cool down to 0°C, stir for 3 hours, filter, And washed with 500 mL of water to obtain 53.6 g of 10-methoxy-4H-benzo[4,5]cycloheptatriene[1,2-b]thiophen-4-one with a yield of 68.6%. The filtrate was concentrated, a solid was precipitated, filtered, rinsed with 100mL of water, and dried to obtain The solid mother liquor 25.8g. The quality of the solid mother liquor is: compound I 58.2%, impurity A 5.5%, impurity B 10.5%, impurity C 8.6%, impurity D 13.4%.

Embodiment 2

[0036] Dissolve 25 g of the solid mother liquor containing 10-methoxy-4H-benzo[4,5]cycloheptatriene[1,2-b]thiophen-4-one obtained in Example 1 in 150mL THF, and then add an appropriate amount of Reductant, heat up reaction, spot plate to follow the reaction process, after the reaction is completed, hot filter, then concentrate to dryness, add ethylene glycol monomethyl ether for recrystallization, and obtain compound I after filtering.

[0037] The yield and purity obtained by different reducing agents are shown in Table 1:

[0038] Table I:

[0039] serial number

reducing agent

Reductant dosage

temperature reflex

Reaction time

Yield

yield b

purity

1

Pd / C a ,H 2

1.2g, 0.5Mpa

55℃

25h

11.3g

45.2％

97.1％

2

Pd / C, hydrazine hydrate

3.7g, 25.0g

55℃

18h

10.1g

40.4％

96.6％

3

Nickel acetate / sodium hydride

8.5g, 6.8g

45℃

8h

8.2g

32.8％

95.7％

4

Zinc pow...

Embodiment 3

[0043] 25g of the solid mother liquor containing 10-methoxy-4H-benzo[4,5]cycloheptatriene[1,2-b]thiophen-4-one obtained in Example 1 was dissolved in 150ml of solvent, and 1.2 g Pd / C, feed 0.5Mpa hydrogen, heat up to 55°C, point the plate and follow the reaction process, after the reaction is completed, heat filter, then concentrate to dryness, add ethylene glycol monomethyl ether for recrystallization, filter, and dry to obtain Compound I.

[0044] The yield and the purity that different reaction solvents obtain are shown in Table 2:

[0045] Table II:

[0046] serial number

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a recycling method of 10-methoxy-4H-benzo[4, 5] cycloheptatriene[1, 2-b] thiophene-4-ketone mother liquid. The method includes: dissolving the mother liquid in an organic solvent, rising temperature, adding a reductant into reaction liquid for reaction, thermally filtering after reaction is finished, concentrating to dryness, adding a crystallizing solvent for crystallization to obtain high-purity 10-methoxy-4H-benzo[4, 5] cycloheptatriene[1, 2-b] thiophene-4-ketone. The method can realize effective recycling of the mother liquid and is easy in control of reaction process and needless of complex special equipment; impurities in the mother liquid are converted through reductive reaction, thereby being able to be separated and purified through a simple crystallizing method.

Description

technical field [0001] The invention relates to a method for recovering a mother liquor containing 10-methoxy-4H-benzo[4,5]cycloheptatriene[1,2-b]thiophen-4-one, which belongs to the field of chemical pharmacy. technical background [0002] Ketotifen fumarate is a powerful oral allergy mediator release agent, which has histamine H1 receptor antagonism and inhibits the release of allergic reaction mediators. It not only has strong anti-allergic effect, but also has a long duration of drug effect. It is more effective in preventing various bronchial asthma attacks and exogenous asthma than endogenous asthma. [0003] 10-methoxy-4H-benzo [4,5] cycloheptatriene [1,2-b] thiophene -4-one is the key intermediate of synthetic ketotifen fumarate, its structure is shown in formula I Show: [0004] [0005] Document Helvetica Chimica Acta, 1976,59 (3), P866-877 discloses the synthetic method of this ketotifen intermediate: by heating the methanol solution of dibromide, adding pota...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D333/80
CPCC07D333/80Y02P20/584
Inventor 张露黄健升徐云超何琦涂国良梁尊俊
Owner LINHAI HUANAN CHEM CO LTD