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Method for preparing lansoprazole midbody

A technology for lansoprazole and an intermediate is applied in the application field of potassium trifluoroethoxide in the preparation of lansoprazole raw materials, and can solve the problems of difficulty in recycling trifluoroethanol, being unsuitable for large-scale production, difficult to separate, and the like , to achieve the effect of less side reactions, high safety and simplified process

Inactive Publication Date: 2008-12-10
李海超
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The defect of this technology is that trifluoroethanol reacts with potassium tert-butoxide to generate potassium trifluoroethoxide while there are a large amount of tert-butanol and a small amount of potassium tert-butoxide, and potassium tert-butoxide also participates in the reaction to produce a small amount of by-products, which can only be obtained through the column. chromatography to remove
In addition, the physical and chemical properties of tert-butanol and trifluoroethanol are similar. The boiling point of tert-butanol is 82.5°C and the boiling point of trifluoroethanol is very close to 73.6°C. , another method for preparing potassium trifluoroethanolate: use trifluoroethanol to directly react with metal potassium, metal potassium floats directly on the liquid surface of trifluoroethanol, is completely exposed to direct contact with the air, the reaction is very violent, even if nitrogen protection It is also very easy to burn and cause fires, and is not suitable for large-scale production. On the basis of known technologies, we have developed a simple, economical and safe method for the production of potassium trifluoroethoxide and lansoprazole

Method used

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  • Method for preparing lansoprazole midbody
  • Method for preparing lansoprazole midbody
  • Method for preparing lansoprazole midbody

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] The bottom is equipped with a 50L stainless steel interlayer reaction kettle with magnetic stirring. It is pre-dried thoroughly. Add 10 liters of hexane and 1.5kg of metal potassium blocks that have been cut in advance. Trifluoroethanol 15L, the rate of addition depends on the severity of the reaction, and the potassium trifluoroethoxide / trifluoroethanol solution generated by the reaction is released from the bottom of the reaction kettle in batches and stored in a sealed container.

Embodiment 2

[0019] Add 6 L of trifluoroethanol to the dry reaction kettle, add 5.0 kg of 2,3-dimethyl-4-nitropyridine-N-oxide and stir to dissolve completely, then add the potassium trifluoroethoxide / Trifluoroethanol solution, heated up to 85-90°C, stirred and reacted for 40 hours, recovered excess trifluoroethanol under reduced pressure, after completion, cooled to room temperature, added water, extracted with chloroform for 4 times, combined chloroform extract and washed with water twice, The chloroform layer was dried over anhydrous sodium sulfate, and the chloroform was evaporated under reduced pressure to obtain 6.2 kg of solid residue, which was directly dissolved by adding 20 L of acetic anhydride and 300 ml of concentrated sulfuric acid, stirred and dissolved, heated to 95-100°C, reacted for 6.0 hours, and the excess was evaporated under reduced pressure Acetic anhydride, add a mixture of methanol, water, and sodium hydroxide (30L: 7.0L: 3.0kg) to make the pH of the solution alkal...

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Abstract

The invention discloses a method for preparing a potassium 2,2,2-trifluoroethanolate which is an intermediate of lansoprazole, and also relates to an application of prepared the potassium 2,2,2-trifluoroethanolate in the preparation of a bulk drug for lansoprazole. The method comprises the following steps that: at a certain temperature, a reaction kettle has a magnetic stirring apparatus at the bottom is pre-dried, and an inert solvent is added into the reaction kettle till the liquid level of the reaction kettle reaches 1 cm above a position where a potassium surface is, cut potassium blocks are added into the reaction kettle in batches and then 2,2,2-trifluoroethyl alcohol is dripped into the reaction kettle; or the 2,2,2-trifluoroethyl alcohol is dripped into the reaction kettle first and then the cut potassium blocks are added into the reaction kettle in batches, the XX produced in the reaction is discharged from the bottom of the kettle in batches. The invention also relates to application of prepared the potassium 2,2,2-trifluoroethanolate in the preparation of a bulk drug for lansoprazole. The method has the advantages of simplification of process, reduction in the production cost of lansoprazole, and obvious economic benefits.

Description

technical field [0001] The present invention relates to a kind of preparation method of potassium trifluoroethoxide of lansoprazole intermediate, also relate to a kind of application of prepared potassium trifluoroethoxide in preparation of lansoprazole crude drug. technical background [0002] Potassium trifluoroethoxide is an important intermediate for the preparation of the acid-suppressing drug proton pump inhibitor lansoprazole, and is also an important raw material for the synthesis of other fluorine-containing compounds. In the preparation method of reported lansoprazole, such as: US6262098; Chem.pharm.bull.38 (10) 2853-2858 (1990). [0003] [0004] Wherein the trifluoroethoxy substitution reaction is to utilize firstly to prepare potassium trifluoroethanolate, then with 2,3-dimethyl-4-nitropyridine-N-oxide generation substitution reaction, purify the product by column chromatography, be used in the next reaction. The defect of this technology is that trifluoroe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C31/38C07C29/70C07D401/12
Inventor 李海超
Owner 李海超