Synthetic method of cis-4-(tetrahydropyrane-2-oxy)-2-butylene-1-ol

Abstract

The invention discloses a synthetic method of cis-4-(tetrahydropyrane-2-oxy)-2-butylene-1-ol. The synthetic method comprises the following steps: performing low-temperature recrystallization and desolution by using acetone on 1,4-butendiol which is taken as a raw material to prepare high-purity cis-1,4-butendiol, then performing addition reaction with 2,3-dihydropyrane under the complex catalysis of toluene-p-sulfonic acid monohydrate and pyridine, and performing desolution to obtain a product namely cis-4-(tetrahydropyrane-2-oxy)-2-butylene-1-ol. The method does not need high-purity cis-1-4-butendiol as a raw material anymore, so that the cost is reduced, the raw material source is broadened, and convenience is provided for industrial production. Moreover, the refining process of butendiol is simple and suitable for scale production. The cis content after refining can be improved to more than or equal to 99.5%. The addition process is simple to operate, and the reaction condition is mild. Methylbenzene extraction and water scrubbing are performed, so that the residues of butendiol are greatly reduced, the product quality is improved, the non-rectification content can reach more than or equal to 80%, and the molar yield to 2,3-dihydropyrane after purification reaches more than or equal to 73%.

Description

technical field

[0001] The invention belongs to the field of organic chemical synthesis, and relates to a synthesis method of a pharmaceutical intermediate, in particular to a synthesis method of cis-4-(tetrahydropyran-2-oxygen)-2-buten-1-ol. Background technique

[0002] Cis-4-(tetrahydropyran-2-oxygen)-2-buten-1-ol is an important intermediate of the drug lafutidine, and is the main side chain of synthetic lafutidine: 4- Key substance of [4-(1-piperidinylmethyl)pyridinyl-2-oxy]-cis-2-butenol.

[0003] Chinese patent (Application No.: 201110333367.1) discloses a synthesis process of a pyranyl monoprotected product of cis-1,4-butenediol. The method is based on cis-1,4-butenediol and dihydrogen Pyran is used as raw material for synthesis, and inorganic salt solution is used as catalyst, mainly sulfate, sulfite and carbonate of sodium and potassium. The above method has the following disadvantages:

[0004] (1) This method uses a large amount of solvent, which is 10 to 20 t...

Images