Purification method of esomeprazole

Abstract

The invention relates to a purification method of esomeprazole. According to the purification method, esomeprazole or salt thereof to be purified is transformed into potassium esomeprazole and then separated by crystallization, and if necessary, the crystallization product is transformed into esomeprazole or salt thereof. Compared with the conventional recrystallization method, the purification method can purify esomeprazole with high efficiency to obtain high-purity esomeprazole or salt thereof. The purification method is particularly suitable for purification of drug compounds with extremely strict requirements on the purity.

Description

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for purifying esomeprazole. Background technique

[0002] Esomeprazole (S)-omeprazole, chemical name: (S)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl Base-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole can effectively inhibit gastric acid secretion and is often used to treat diseases related to gastric acid secretion disorders, such as gastric ulcer and duodenal ulcer. This compound has the following structural formula:

[0003]

[0004] In the prior art, esomeprazole is usually prepared by oxidative resolution or asymmetric oxidation of thioether. Since the oxidation process is difficult to control, the formation of various by-products cannot be avoided. For example, when thioether is oxidized to sulfoxide It is further oxidized to sulfone. Contents of the invention

[0005] The object of the present invention is to provide a kind of purification method of esomeprazole, ...

Examples

Embodiment 1

[0032] Embodiment 1: the purification of esomeprazole sodium salt

[0033] Add 30g (81.7mmol) of esomeprazole sodium salt (3.04% sulfone content) into the reaction flask, add 150ml of methanol, heat to 50°C, add 6.9g (98.0mmol) of potassium methoxide, immediately precipitate a white solid, and heat to reflux for 1h , cooled to room temperature and stirred for 1 h, suction filtered, washed and dried, yield: 30 g (containing 12.1% methanol), methanol was removed by vacuum drying (sulfone content 0.98%).

Embodiment 2

[0034] Embodiment 2: the purification of esomeprazole sodium salt

[0035] Add 30g (81.7mmol) of esomeprazole sodium salt (sulfone content 3.04%) into the reaction flask, add 150ml of methanol, heat to 50°C, add 5.5g (98.0mmol) of potassium hydroxide, heat to reflux for 1h, and cool to room temperature Stirring for 1 h, suction filtration, washing and drying, yield: 28 g (containing 11.8% methanol), vacuum drying to remove methanol (sulfone content 1.12%).

Embodiment 3

[0036] Embodiment 3: the purification of esomeprazole triethylamine salt

[0037] Add 36.5g (82mmol) of esomeprazole triethylamine salt (sulfone content 2.93%) into the reaction flask, add 150ml of methanol, heat to 50°C, add 6.9g (98.0mmol) of potassium methylate, and immediately precipitate a white solid, heat to reflux 1h, cooled to room temperature and stirred for 1h, suction filtered, washed and dried, yield: 27g (containing 12.0% methanol), and vacuum dried to remove methanol (sulfone content: 1.04%).

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a method for purifying esomeprazole. Background technique

[0002] Esomeprazole (S)-omeprazole, chemical name: (S)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl Base-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole can effectively inhibit gastric acid secretion and is often used to treat diseases related to gastric acid secretion disorders, such as gastric ulcer and duodenal ulcer. This compound has the following structural formula:

[0003]

[0004] In the prior art, esomeprazole is usually prepared by oxidative resolution or asymmetric oxidation of thioether. Since the oxidation process is difficult to control, the formation of various by-products cannot be avoided. For example, when thioether is oxidized to sulfoxide It is further oxidized to sulfone. Contents of the invention

[0005] The object of the present invention is to provide a kind of purification method of esomeprazole, ...

Examples

Embodiment 1

[0032] Embodiment 1: the purification of esomeprazole sodium salt

[0033] Add 30g (81.7mmol) of esomeprazole sodium salt (3.04% sulfone content) into the reaction flask, add 150ml of methanol, heat to 50°C, add 6.9g (98.0mmol) of potassium methoxide, immediately precipitate a white solid, and heat to reflux for 1h , cooled to room temperature and stirred for 1 h, suction filtered, washed and dried, yield: 30 g (containing 12.1% methanol), methanol was removed by vacuum drying (sulfone content 0.98%).

Embodiment 2

[0034] Embodiment 2: the purification of esomeprazole sodium salt

[0035] Add 30g (81.7mmol) of esomeprazole sodium salt (sulfone content 3.04%) into the reaction flask, add 150ml of methanol, heat to 50°C, add 5.5g (98.0mmol) of potassium hydroxide, heat to reflux for 1h, and cool to room temperature Stirring for 1 h, suction filtration, washing and drying, yield: 28 g (containing 11.8% methanol), vacuum drying to remove methanol (sulfone content 1.12%).

Embodiment 3

[0036] Embodiment 3: the purification of esomeprazole triethylamine salt

[0037] Add 36.5g (82mmol) of esomeprazole triethylamine salt (sulfone content 2.93%) into the reaction flask, add 150ml of methanol, heat to 50°C, add 6.9g (98.0mmol) of potassium methylate, and immediately precipitate a white solid, heat to reflux 1h, cooled to room temperature and stirred for 1h, suction filtered, washed and dried, yield: 27g (containing 12.0% methanol), and vacuum dried to remove methanol (sulfone content: 1.04%).

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