Method for refining prolinamide

Abstract

The invention relates to a method for refining prolinamide, which includes the following steps: (a) dissolving prolinamide coarse product in an organic solvent, wherein the prolinamide coarse product contains ammonium chloride, prolinamide hydrochloride or mixture thereof; (b) adding inorganic alkali for treatment; and (c) separating to obtain the prolinamide. The method for refining prolinamide is simple, the content and optical purity of the obtained product are high, and the method is very suitable for industrial production.

Description

field of invention

[0001] The invention relates to a method for refining prolineamide. Background technique

[0002] Both L-prolinamide and D-prolinamide are important optically active pyrrole derivatives with excellent asymmetry source properties, and have been more and more widely used in the synthesis of end groups of polypeptide compounds. For example, L-prolineamide can be used as a key intermediate in the synthesis of vildagliptin, a drug for treating diabetes, and D-prolineamide can be used in the synthesis of antitumor drugs such as platinum compound (CDDP) and neuroleptic. In addition, these two compounds are often used as resolving agents and chiral reagents. Therefore, prolinamide, as a fine organic chemical intermediate of optically active pyrrole derivatives, is widely used in the fields of medicine, pesticide, chemical industry and the like.

[0003] At present, there are two main routes for the synthesis of prolineamide:

[0004] Route 1: Kazumi et al. (Jou...

Examples

Embodiment 1

[0029] Embodiment 1: Preparation of L-proline methyl ester hydrochloride.

[0030] Pump 500L of methanol into the reactor, and drop in 100 kg of L-proline. Stir and cool to 0~-10°C, and add 136 kg of thionyl chloride dropwise under temperature control. After dropping, the temperature was raised to reflux for 1 to 2 hours. Methanol was concentrated under reduced pressure to obtain a yellow oil.

Embodiment 2

[0031] Embodiment 2: Preparation of D-proline methyl ester hydrochloride.

[0032] Pump 500L of methanol into the reactor, and drop in 100 kg of D-proline. Stir and cool to 0~-10°C, and add 136 kg of thionyl chloride dropwise under temperature control. After dropping, the temperature was raised to reflux for 1 to 2 hours. Methanol was concentrated under reduced pressure to obtain a yellow oil.

Embodiment 3

[0033] Embodiment 3: Preparation of D-proline ethyl ester hydrochloride.

[0034] Pump 500L of ethanol into the reactor, and drop in 100 kg of D-proline. Stir and cool to 0~-10°C, and add 136 kg of thionyl chloride dropwise under temperature control. After dropping, the temperature was raised to reflux for 1 to 2 hours. Ethanol was concentrated under reduced pressure to obtain a yellow oil.

[0035] step 2

[0036]

field of invention

[0001] The invention relates to a method for refining prolineamide. Background technique

[0002] Both L-prolinamide and D-prolinamide are important optically active pyrrole derivatives with excellent asymmetry source properties, and have been more and more widely used in the synthesis of end groups of polypeptide compounds. For example, L-prolineamide can be used as a key intermediate in the synthesis of vildagliptin, a drug for treating diabetes, and D-prolineamide can be used in the synthesis of antitumor drugs such as platinum compound (CDDP) and neuroleptic. In addition, these two compounds are often used as resolving agents and chiral reagents. Therefore, prolinamide, as a fine organic chemical intermediate of optically active pyrrole derivatives, is widely used in the fields of medicine, pesticide, chemical industry and the like.

[0003] At present, there are two main routes for the synthesis of prolineamide:

[0004] Route 1: Kazumi et al. (Jou...

Examples

Embodiment 1

[0029] Embodiment 1: Preparation of L-proline methyl ester hydrochloride.

[0030] Pump 500L of methanol into the reactor, and drop in 100 kg of L-proline. Stir and cool to 0~-10°C, and add 136 kg of thionyl chloride dropwise under temperature control. After dropping, the temperature was raised to reflux for 1 to 2 hours. Methanol was concentrated under reduced pressure to obtain a yellow oil.

Embodiment 2

[0031] Embodiment 2: Preparation of D-proline methyl ester hydrochloride.

[0032] Pump 500L of methanol into the reactor, and drop in 100 kg of D-proline. Stir and cool to 0~-10°C, and add 136 kg of thionyl chloride dropwise under temperature control. After dropping, the temperature was raised to reflux for 1 to 2 hours. Methanol was concentrated under reduced pressure to obtain a yellow oil.

Embodiment 3

[0033] Embodiment 3: Preparation of D-proline ethyl ester hydrochloride.

[0034] Pump 500L of ethanol into the reactor, and drop in 100 kg of D-proline. Stir and cool to 0~-10°C, and add 136 kg of thionyl chloride dropwise under temperature control. After dropping, the temperature was raised to reflux for 1 to 2 hours. Ethanol was concentrated under reduced pressure to obtain a yellow oil.

[0035] step 2

[0036]

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