Preparation method of chiral 1-amino-2-propanol

A chiral and amino technology, which is applied in the preparation of amino hydroxyl compounds, organic compounds, organic chemical methods, etc., can solve the problems of unfavorable environmental protection, waste acid, waste alkali and waste gas, and achieve convenient operation, high purity and Yield, the effect of simplifying the preparation process

CN111574384AActive Publication Date: 2020-08-25SHANGHAI BALMXY PHARMA CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2020-08-25

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Abstract

The invention provides a preparation method of chiral 1-amino-2-propanol, which comprises the following steps: carrying out ring-opening reaction on trifluoroacetamide and chiral epoxypropane to generate an intermediate product I; and carrying out hydrolysis reaction on the intermediate product I to obtain the chiral 1-amino-2-propanol. According to the preparation method, the target product can be obtained through a two-step reaction, so that the preparation process of chiral 1-amino-2-propanol is greatly simplified; and the raw materials trifluoroacetamide and chiral epoxypropane are cheap and easily available, the reaction process is simple, the operation is convenient, harsh reaction conditions such as high temperature and high pressure are not needed, complex purification, post-treatment and chiral resolution operations are also not needed, and the obtained target product has high purity, high yield and high optical activity, and is suitable for large-scale industrial preparation.
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Description

Technical field

[0001] The invention belongs to the technical field of organic compound synthesis, and specifically relates to a preparation method of chiral 1-amino-2-propanol. Background technique

[0002] 1-Amino-2-propanol is widely used in the fields of fine chemicals and biomedicine. It is the raw material for the production of surfactants, textile auxiliaries, detergents, dye auxiliaries and dispersants. It is also used for the preparation of medicines and pesticides. Important synthetic intermediate. Among them, chiral 1-amino-2-propanol is an intermediate for the synthesis of anti-AIDS drugs Tenofovir and other nucleoside drugs, and it also has important applications in the development of other new drugs and new materials. Due to the wide application of 1-amino-2-propanol, especially chiral 1-amino-2-propanol in the chemical and pharmaceutical fields, its demand has also increased accordingly. Therefore, the preparation of such compounds has been continuously studied an...

Examples

Embodiment 1

[0053] A preparation method of (S)-1-amino-2-propanol, which specifically includes the following steps:

[0054] (1)

[0055] Dissolve sodium tert-butoxide (230g, 2.39mol) in tetrahydrofuran (2L), slowly add trifluoroacetamide (226g, 2mol) under ice bath, stir for 30min; then add (S)-propylene oxide under ice bath (128g, 2.2mol), naturally warm up to room temperature, continue to stir the reaction for 10h, and then stir for another 2h at 35℃; after the reaction, add 1L of 2N (equivalent concentration) hydrochloric acid to the system for neutralization, and then add 1L of water. After standing for separation, the aqueous phase was extracted with dichloromethane, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 318 g of intermediate product I with a yield of 93%.

[0056] Intermediate I 1 H-NMR(CDCl 3 , 400MHz): δ 1.08 (d, 3H), 3.37 (m, 2H), 4.0 (m, 1H), 7.12 (brs, 1H).

[0057] (2)

[0058] Dissolve the intermedi...

Embodiment 2

[0061] A method for preparing (R)-1-amino-2-propanol, specifically including the following steps:

[0062] (1)

[0063] Dissolve sodium tert-butoxide (300g, 3.12mol) in tetrahydrofuran (2L), slowly add trifluoroacetamide (294g, 2.6mol) under ice bath, stir for 30min; then add (R)-epoxy under ice bath Propane (166g, 2.96mol), naturally warm to room temperature, continue to stir and react for 10h, and then stir for 2h at 35℃; after the reaction, add 2N (equivalent concentration) hydrochloric acid to the system for neutralization, and then add water 1.3L, stand for layering, extract the aqueous phase with dichloromethane, combine the organic phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain 423 g of intermediate product I with a yield of 95%.

[0064] Intermediate I 1 H-NMR(CDCl 3 , 400MHz): δ 1.07 (d, 3H), 3.36 (m, 2H), 3.99 (m, 1H), 7.11 (brs, 1H).

[0065] (2)

[0066] Dissolve the intermediate product I (420g, 2.45mol) obtained in step (1) ...

Embodiment 3

[0069] A method for preparing (R)-1-amino-2-propanol, specifically including the following steps:

[0070] (1)

[0071] Dissolve potassium tert-butoxide (303g, 2.7mol) in N,N-dimethylformamide (2L), slowly add trifluoroacetamide (282.5g, 2.5mol) under ice bath, and stir for 30min; Add (R)-propylene oxide (147.9g, 2.55mol) under the bath, naturally warm to room temperature, continue to stir and react for 6.5h, and then stir for another 1.5h at 35°C; after the reaction, add 2N (equivalent concentration) to the system. Neutralize with 0.8L of hydrochloric acid, then add 0.8L of water, stand to separate the layers, extract the aqueous phase with dichloromethane, combine the organic phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain 398g of intermediate product I. The rate is 93%.

[0072] (2)

[0073] Intermediate product I (390g, 2.28mol) obtained in step (1) was dissolved in methanol (1.5L), 350mL of water and sodium carbonate (477g, 4.5mol) ...