The preparation method of 2-fluoroethylamine hydrochloride

Abstract

The invention discloses a preparation method of 2-fluoroethylamine hydrochloride, the method steps are as follows: S1: Synthesis of 2-fluoroethyl phthalimide; adding 2-fluoro-1-halogen Ethane and potassium phthalimide are dissolved with N,N-dimethylformamide under mechanical stirring, and reacted. After the reaction is completed, N,N-dimethylformamide is recovered by distillation under reduced pressure, and then supplied to Add water into the reaction vessel, heat and stir, and obtain 2-fluoroethyl phthalimide intermediate after cooling, filtering and vacuum drying; S2: Synthesis of 2-fluoroethylamine hydrochloride; in the reaction vessel Add the 2-fluoroethyl phthalimide intermediate prepared in S1 and dissolve it with ethanol, then add hydrazine hydrate dropwise for reaction, cool down after the reaction, adjust the pH to 5 with hydrochloric acid, reflux for 1 hour, and filter , vacuum drying to obtain white flaky crystal 2-fluoroethylamine hydrochloride. The method of the invention has the advantages of simple process, green safety, low cost and high output.

Description

technical field

[0001] The invention relates to the technical field of chemical industry, in particular to a preparation method of 2-fluoroethylamine hydrochloride. Background technique

[0002] 2-Fluoroethylamine is a very important pharmaceutical intermediate, and its hydrochloride is generally available in the market, namely 2-fluoroethylamine hydrochloride. With the important role in the field of medicine and the successful development and launch of related drugs, the market demand for 2-fluoroethylamine hydrochloride is also increasing day by day. How to prepare 2-fluoroethylamine hydrochloride in a green, fast, safe, stable and low-cost manner has become an urgent problem to be solved.

[0003] Danny C. Lenstra, Peter E. Lenting and Jasmin et al (Green Chem., 2018, 20, 4418-4422) Danny C. Lenstra, Joris J. Wolf, and Jasmin (J.Org.Chem.2019, 84, 6536-6545) Using azide intermediates as raw materials, the desired amino compounds are prepared by reacting with tripheny...

Examples

Embodiment 1

[0022] The preparation method of 2-fluoroethylamine hydrochloride proposed by the present invention, the method steps are as follows:

[0023] (1) Synthesis of 2-fluoroethane phthalimide: add 254g (2mol) of 2-fluoro-1-bromoethane and 380g (2.05mol) of phthalate in a 2L reaction vessel Potassium imide, dissolved with 1.5L of N,N-dimethylformamide (DMF) under mechanical stirring, heated to 100°C for 8h reaction, distilled under reduced pressure, the amount of DMF recovered was 1.3L, and 1.3L of water was added After stirring, a large amount of white solids were precipitated, filtered, and the filter cake was rinsed twice with 300 mL of water, and dried in vacuo to obtain 340 g (1.76 mol) of the intermediate 2-fluoroethane phthalimide with a yield of 88%.

[0024] (2) Synthesis of 2-fluoroethylamine hydrochloride: 340 g (1.76 mol) of the 2-fluoroethyl phthalimide intermediate prepared in S1 was added to a 3 L reaction vessel and stirred with 2L of ethanol was dissolved, then 121...

Embodiment 2

[0026] (1) Synthesis of 2-fluoroethane phthalimide: 254 g (2 mol) of 2-fluoro-1-bromoethane and 296.5 g (1.6 mol) of phthalic acid were added to a 2L reaction vessel Potassium carboximide, dissolved with 1.5L of N,N-dimethylformamide (DMF) under mechanical stirring, heated to 100°C for 8h reaction, distilled under reduced pressure, the amount of DMF recovered was 1.3L, 1.3L was added After stirring with water, a large amount of white solids were precipitated, filtered, and the filter cake was rinsed twice with 300 mL of water, and dried under vacuum to obtain 289 g (1.495 mol) of intermediate 2-fluoroethane phthalimide with a yield of 75%.

[0027] (2) Synthesis of 2-fluoroethylamine hydrochloride: 289 g (1.495 mol) of the 2-fluoroethane phthalimide intermediate prepared in S1 was added to a 3L reaction vessel and stirred with a mechanical 1.7L of ethanol was dissolved, then 74.8g (1.2mol) of 80% hydrazine hydrate was added dropwise, the temperature was raised to 50°C for reac...

Embodiment 3

[0029] (1) Synthesis of 2-fluoroethane phthalimide: 254g (2mol) of 2-fluoro-1-bromoethane and 407.4g (2.2mol) of phthalate were added to a 2L reaction vessel Potassium carboximide, dissolved with 1.7L of N,N-dimethylformamide (DMF) under mechanical stirring, heated to 100°C for 8h reaction, distilled under reduced pressure, the amount of DMF recovered was 1.5L, 1.5L was added Water was stirred to precipitate a large amount of white solids, filtered, and the filter cake was rinsed twice with 300 mL of water, and dried in vacuo to obtain 347.7 g (1.8 mol) of 2-fluoroethane phthalimide intermediate, with a yield of 90%. .

[0030] (2) Synthesis of 2-fluoroethylamine hydrochloride: 347.7 g (1.8 mol) of the 2-fluoroethane phthalimide intermediate prepared in S1 was added to a 3L reaction vessel and stirred under mechanical stirring. Dissolve with 2.2L ethanol, then add dropwise 123.7g (1.98mol) of 80% hydrazine hydrate, heat up to 50°C for reaction 1h, then heat up to reflux for 8...

technical field

[0001] The invention relates to the technical field of chemical industry, in particular to a preparation method of 2-fluoroethylamine hydrochloride. Background technique

[0002] 2-Fluoroethylamine is a very important pharmaceutical intermediate, and its hydrochloride is generally available in the market, namely 2-fluoroethylamine hydrochloride. With the important role in the field of medicine and the successful development and launch of related drugs, the market demand for 2-fluoroethylamine hydrochloride is also increasing day by day. How to prepare 2-fluoroethylamine hydrochloride in a green, fast, safe, stable and low-cost manner has become an urgent problem to be solved.

[0003] Danny C. Lenstra, Peter E. Lenting and Jasmin et al (Green Chem., 2018, 20, 4418-4422) Danny C. Lenstra, Joris J. Wolf, and Jasmin (J.Org.Chem.2019, 84, 6536-6545) Using azide intermediates as raw materials, the desired amino compounds are prepared by reacting with tripheny...

Examples

Embodiment 1

[0022] The preparation method of 2-fluoroethylamine hydrochloride proposed by the present invention, the method steps are as follows:

[0023] (1) Synthesis of 2-fluoroethane phthalimide: add 254g (2mol) of 2-fluoro-1-bromoethane and 380g (2.05mol) of phthalate in a 2L reaction vessel Potassium imide, dissolved with 1.5L of N,N-dimethylformamide (DMF) under mechanical stirring, heated to 100°C for 8h reaction, distilled under reduced pressure, the amount of DMF recovered was 1.3L, and 1.3L of water was added After stirring, a large amount of white solids were precipitated, filtered, and the filter cake was rinsed twice with 300 mL of water, and dried in vacuo to obtain 340 g (1.76 mol) of the intermediate 2-fluoroethane phthalimide with a yield of 88%.

[0024] (2) Synthesis of 2-fluoroethylamine hydrochloride: 340 g (1.76 mol) of the 2-fluoroethyl phthalimide intermediate prepared in S1 was added to a 3 L reaction vessel and stirred with 2L of ethanol was dissolved, then 121...

Embodiment 2

[0026] (1) Synthesis of 2-fluoroethane phthalimide: 254 g (2 mol) of 2-fluoro-1-bromoethane and 296.5 g (1.6 mol) of phthalic acid were added to a 2L reaction vessel Potassium carboximide, dissolved with 1.5L of N,N-dimethylformamide (DMF) under mechanical stirring, heated to 100°C for 8h reaction, distilled under reduced pressure, the amount of DMF recovered was 1.3L, 1.3L was added After stirring with water, a large amount of white solids were precipitated, filtered, and the filter cake was rinsed twice with 300 mL of water, and dried under vacuum to obtain 289 g (1.495 mol) of intermediate 2-fluoroethane phthalimide with a yield of 75%.

[0027] (2) Synthesis of 2-fluoroethylamine hydrochloride: 289 g (1.495 mol) of the 2-fluoroethane phthalimide intermediate prepared in S1 was added to a 3L reaction vessel and stirred with a mechanical 1.7L of ethanol was dissolved, then 74.8g (1.2mol) of 80% hydrazine hydrate was added dropwise, the temperature was raised to 50°C for reac...

Embodiment 3

[0029] (1) Synthesis of 2-fluoroethane phthalimide: 254g (2mol) of 2-fluoro-1-bromoethane and 407.4g (2.2mol) of phthalate were added to a 2L reaction vessel Potassium carboximide, dissolved with 1.7L of N,N-dimethylformamide (DMF) under mechanical stirring, heated to 100°C for 8h reaction, distilled under reduced pressure, the amount of DMF recovered was 1.5L, 1.5L was added Water was stirred to precipitate a large amount of white solids, filtered, and the filter cake was rinsed twice with 300 mL of water, and dried in vacuo to obtain 347.7 g (1.8 mol) of 2-fluoroethane phthalimide intermediate, with a yield of 90%. .

[0030] (2) Synthesis of 2-fluoroethylamine hydrochloride: 347.7 g (1.8 mol) of the 2-fluoroethane phthalimide intermediate prepared in S1 was added to a 3L reaction vessel and stirred under mechanical stirring. Dissolve with 2.2L ethanol, then add dropwise 123.7g (1.98mol) of 80% hydrazine hydrate, heat up to 50°C for reaction 1h, then heat up to reflux for 8...

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