A kind of preparation method of 1-amino-1-cyclopentylmethanol

Abstract

The invention provides a method for preparing 1-amino-1-cyclopentylmethanol, the method comprising the following steps: mixing cycloleucine, sodium borohydride, iodine and tetrahydrofuran for reaction, desolventizing after the reaction, mixing with palladium carbon for reflux, and then post-processing to obtain the 1-amino-1-cyclopentylmethanol. The preparation method provided by the invention has mild reaction conditions, high yield, simple post-processing, high product purity, and is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a method for preparing 1-amino-1-cyclopentylmethanol, and in particular to a method for preparing 1-amino-1-cyclopentylmethanol with high purity. Background Art

[0002] 1-Amino-1-cyclopentylmethanol plays an important role in various commercial and consumer products. As a key organic synthesis intermediate, it is used in the research and development of new drugs and special chemical product intermediates. It can also be used to prepare amino acids and other biologically active compounds and material additives. 1-Amino-1-cyclopentylmethanol is also commonly used in the preparation of leveling agents. It can be used for dyeing wool, silk, and nylon with acid dyes. It plays an important role in improving the product quality of printing and dyeing factories and preventing color spots.

[0003] CN104926747B discloses a method for synthesizing an optically active cycloalkyloxazoline ligand and its use, wherein a method for preparing 1-amino-1-cyclopentylmethanol by reacting cycloleucine and lithium aluminum hydride is disclosed, but lithium aluminum hydride has high reactivity and high risk, and is not suitable for industrial production. In addition, the post-processing of the reaction with lithium aluminum hydride is complicated, and the product purity is not high.

[0004] Therefore, how to provide a method for preparing 1-amino-1-cyclopentylmethanol with high purity and good yield has become a problem to be solved urgently. Summary of the invention

[0005] In view of the deficiencies in the prior art, the object of the present invention is to provide a method for preparing 1-amino-1-cyclopentylmethanol, and in particular to provide a method for preparing 1-amino-1-cyclopentylmethanol with high purity. The preparation method provided by the present invention has mild reaction conditions, high yield, simple post-treatment, high product purity, and is suitable for industrial production.

[0006] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0007] The present invention provides a method for preparing 1-amino-1-cyclopentylmethanol, which comprises the following steps:

[0008] Cycloleucine, sodium borohydride, iodine and tetrahydrofuran are mixed for reaction, and after the reaction, the mixture is desolvated and mixed with palladium carbon for reflux, followed by post-treatment to obtain the 1-amino-1-cyclopentylmethanol.

[0009] The above method can effectively reduce the requirements for reaction conditions by using sodium borohydride instead of lithium aluminum tetrahydride in the conventional method, and after the reaction is completed, the reaction solvent is removed and then refluxed with palladium carbon for reaction, which can effectively reduce the amount of palladium carbon added and save a lot of raw materials and costs; at the same time, the post-processing is simple, the yield is high, the product purity is high, and it is suitable for industrial production.

[0010] Preferably, the molar ratio of cycloleucine, sodium borohydride and iodine is 1:(4-8):(2.5-3.5).

[0011] Preferably, the reaction temperature is 20-30°C and the reaction time is 20-28h.

[0012] Wherein, the molar ratio of cycloleucine, sodium borohydride and iodine can be 1:4:2.5, 1:5:2.7, 1:6:3, 1:7:3.2 or 1:8:3.5, etc., the reaction temperature can be 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C or 30°C, etc., and the reaction time can be 20h, 21h, 22h, 23h, 24h, 25h, 26h, 27h or 28h, etc., but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are equally applicable.

[0013] Preferably, after the reaction is completed, a quencher is added to quench the reaction, and the quencher includes alcohol, and the alcohol includes methanol and / or ethanol.

[0014] Preferably, the reflux is performed in a solvent, the solvent comprises an alcohol, and the alcohol comprises methanol and / or ethanol.

[0015] Preferably, the alcohol is methanol.

[0016] The above-mentioned specific alcohol can effectively dissolve the reaction raw materials and products, increase the speed of the subsequent treatment process, and shorten the treatment time.

[0017] Preferably, the mass ratio of cycloleucine to palladium carbon is 1:(0.05-0.1), and the mass fraction of palladium carbon is 5-15%.

[0018] Preferably, the reflux time is 40-50h.

[0019] Among them, the mass ratio of cycloleucine and palladium carbon can be 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09 or 1:0.7, etc., and the mass fraction of palladium carbon can be 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14% or 15%, etc., but is not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are equally applicable.

[0020] Preferably, the post-treatment comprises the following steps: filtering the refluxed product and drying it in a rotary dryer, dissolving the dried product with a solvent, filtering it, and drying the filtrate again to obtain the 1-amino-1-cyclopentylmethanol.

[0021] Preferably, the solvent comprises dichloromethane and / or ethyl acetate.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The invention provides a method for preparing 1-amino-1-cyclopentylmethanol. By adopting sodium borohydride to replace lithium aluminum tetrahydride in a conventional method, the requirements for reaction conditions can be effectively reduced. After the reaction is completed, the reaction solvent is removed and then refluxed with palladium carbon for reaction, which can effectively reduce the amount of palladium carbon added and save a large amount of raw materials and costs. At the same time, the post-treatment is simple, the yield is high, the product purity is high, and it is suitable for industrial production. DETAILED DESCRIPTION

[0024] In order to further explain the technical means and effects adopted by the present invention, the technical solution of the present invention is further described below in conjunction with the preferred embodiments of the present invention, but the present invention is not limited to the scope of the embodiments.

[0025] Example 1

[0026] This embodiment provides a method for preparing 1-amino-1-cyclopentylmethanol, and the specific steps are as follows:

[0027] Dissolve cycloleucine (148g) and sodium borohydride (260g) in 2500mL of tetrahydrofuran, slowly add iodine (872.6g) to the system in batches under ice bath conditions, and stir at 25°C for 24h. TLC spot plate, ninhydrin color development confirms that the reaction is complete, then add methanol to quench the reaction under ice bath, spin dry, add methanol to dissolve, add 10.4g Pd / C (10%) and reflux for 48h, then filter to remove Pd / C, spin dry, and dissolve with dichloromethane, salt will precipitate, filter to remove salt to obtain a clear and transparent filtrate, spin dry to obtain 95g of product, yield 72%, purity 98% (GCMS detection). Characterization data are as follows: 1 H NMR (400MHz, dmso) δ3.20 (d, J = 17.4Hz 2H), 1.73-1.26 (m 8H).

[0028] Example 2

[0029] This embodiment provides a method for preparing 1-amino-1-cyclopentylmethanol, and the specific steps are as follows:

[0030] Cycloleucine (148 g) and sodium borohydride (174 g) were dissolved in 2500 mL of tetrahydrofuran, and iodine (730 g) was slowly added to the system in batches under ice bath conditions, and stirred at 20°C for 28 h. TLC spot plate, ninhydrin color development confirmed the completion of the reaction, and then ethanol was added to quench the reaction under ice bath, spin dried, added ethanol to dissolve, 7.4 g Pd / C (10%) was added and refluxed for 50 h, and then Pd / C was filtered out, spin dried, and dissolved in ethyl acetate, salts were precipitated, and the salts were filtered out to obtain a clear and transparent filtrate, which was spin dried to obtain 93.3 g of the product, with a yield of 70% and a purity of 97% (GCMS detection).

[0031] Example 3

[0032] This embodiment provides a method for preparing 1-amino-1-cyclopentylmethanol, and the specific steps are as follows:

[0033] Cycloleucine (148 g) and sodium borohydride (348 g) were dissolved in 3000 mL of tetrahydrofuran, and iodine (1022 g) was slowly added to the system in batches under ice bath conditions, and stirred at 30°C for 20 h. TLC spot plate, ninhydrin color development confirmed the completion of the reaction, and then methanol was added to quench the reaction under ice bath, spin dried, methanol was added to dissolve, 14.8 g of Pd / C (10%) was added and refluxed for 40 h, and then Pd / C was filtered out, spin dried, and dissolved in dichloromethane, salts would precipitate, and the salts were filtered out to obtain a clear and transparent filtrate, which was spin dried to obtain 94.6 g of the product, with a yield of 71% and a purity of 97% (GCMS detection).

[0034] Example 4

[0035] This embodiment provides a method for preparing 1-amino-1-cyclopentylmethanol, and the specific steps are as follows:

[0036] Dissolve cycloleucine (148g) and sodium borohydride (260g) in 2500mL of tetrahydrofuran, slowly add iodine (872.6g) to the system in batches under ice bath conditions, and stir at 25°C for 24h. TLC spot plate, ninhydrin color development confirms that the reaction is complete, then add methanol to quench the reaction under ice bath, spin dry, add methanol to dissolve, add 88.8g Pd / C (10%) and reflux for 48h, then filter to remove Pd / C, spin dry, and dissolve with dichloromethane, salt will precipitate, filter to remove salt to obtain a clear and transparent filtrate, spin dry, and obtain 96.3g of product, with a yield of 73% and a purity of 98% (GCMS detection). Characterization data are as follows: 1 H NMR (400MHz, dmso) δ3.20 (d, J = 17.4Hz 2H), 1.73-1.26 (m 8H).

[0037] Comparative Example 1

[0038] This comparative example provides a method for preparing 1-amino-1-cyclopentylmethanol, and the specific steps are as follows:

[0039] Dissolve cycloleucine (148 g) and sodium borohydride (260 g) in 2500 mL of tetrahydrofuran, slowly add iodine (872.6 g) to the system in batches under ice bath conditions, and stir at 25°C for 24 h. TLC spot plate, ninhydrin color development confirms that the reaction is complete, then methanol is added to quench the reaction under ice bath, then 10.4 g Pd / C (10%) is added and refluxed for 48 h, then Pd / C is filtered out, spin-dried, and dissolved in dichloromethane, salt will precipitate, filter out the salt to obtain 99 g of product, yield 63.5%, purity 83% (GCMS detection).

[0040] Comparative Example 2

[0041] This comparative example provides a method for preparing 1-amino-1-cyclopentylmethanol, and the specific steps are as follows:

[0042] Cycloleucine (148 g) and sodium borohydride (260 g) were dissolved in 2500 mL of tetrahydrofuran, and iodine (872.6 g) was slowly added to the system in batches under ice bath conditions, and stirred at 25°C for 24 h. TLC spot plate, ninhydrin color development confirmed the completion of the reaction, and then methanol was added to quench the reaction under ice bath, and then 88.8 g of Pd / C (10%) was added to reflux for 48 h, and then Pd / C was filtered out, dried, and dissolved in dichloromethane, and salt was precipitated. The salt was filtered out to obtain 105.4 g of the product, with a yield of 66% and a purity of 81% (GCMS detection).

[0043] Comparative Example 3

[0044] This comparative example provides a method for preparing 1-amino-1-cyclopentylmethanol, and the specific steps are as follows:

[0045] Cycloleucine (4 g) was dissolved in 50 mL of tetrahydrofuran, and lithium aluminum tetrahydride (2.4 g) was slowly added to the system in batches under ice-salt bath conditions, and stirred at 0°C for 1 h. TLC spot plate, ninhydrin color development confirmed the completion of the reaction, and then sodium sulfate decahydrate was added under ice bath to quench the reaction, stirred for one hour after addition, and then filtered, the filter cake was washed with tetrahydrofuran, and the filtrate was evaporated to dryness to obtain 2.73 g of brown oily product, with a yield of 55.2% and a purity of 72% (GCMS detection).

[0046] The above results show that the preparation method provided by the present invention can be used for the simple and efficient synthesis of 1-amino-1-cyclopentylmethanol; by comparing Example 1 and Comparative Examples 1-2, it can be found that in Example 1, the amount of palladium carbon added can be effectively reduced by removing the reaction solvent after the reaction is completed and then refluxing with palladium carbon, thereby saving a large amount of raw materials and costs, while the palladium carbon is directly added for reflux without removing the reaction solvent, and more palladium carbon needs to be added to barely achieve a similar effect; by comparing Example 1 and Comparative Example 3, it can be found that compared with the conventional method, the present invention has not only milder reaction conditions and safer reactions, but also higher product purity; by comparing Examples 1 and 4, it can be found that although increasing the amount of palladium carbon can increase the yield, the increase is small, and a large amount of palladium carbon needs to be added, which is costly, while in Example 1, only a small amount of palladium carbon is required to achieve high yield and high purity 1-amino-1-cyclopentylmethanol preparation, which significantly reduces the cost.

[0047] The applicant declares that the present invention illustrates the preparation method of 1-amino-1-cyclopentylmethanol of the present invention through the above-mentioned embodiment, but the present invention is not limited to the above-mentioned embodiment, that is, it does not mean that the present invention must rely on the above-mentioned embodiment to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0048] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0049] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A method for preparing 1-amino-1-cyclopentylmethanol, characterized in that: The preparation method comprises the following steps: Cycloleucine, sodium borohydride, iodine and tetrahydrofuran are mixed for reaction, and after the reaction, the mixture is desolvated and then mixed with palladium carbon for reflux, followed by post-treatment to obtain the 1-amino-1-cyclopentylmethanol; The reaction temperature is 20-30°C and the reaction time is 20-28h; The mass ratio of the cycloleucine to palladium carbon is 1:(0.05-0.1), and the mass fraction of the palladium carbon is 5-15%.

2. The preparation method according to claim 1, characterized in that: The molar ratio of cycloleucine, sodium borohydride and iodine is 1:(4-8):(2.5-3.5).

3. The preparation method according to claim 1, characterized in that: After the reaction is completed, a quencher is added to quench the reaction, and the quencher is methanol and / or ethanol.

4. The preparation method according to claim 1, characterized in that: The reflux is carried out in a solvent, and the solvent is methanol and / or ethanol.

5. The preparation method according to claim 4, characterized in that: The alcohol is methanol.

6. The preparation method according to claim 1, characterized in that: The reflux time is 40-50h.

7. The preparation method according to claim 1, characterized in that: The post-treatment comprises the following steps: filtering the refluxed product and drying it by spin drying, dissolving the dried product with a solvent, filtering it, and drying the filtrate again to obtain the 1-amino-1-cyclopentylmethanol.

8. The preparation method according to claim 7, characterized in that: The solvent is dichloromethane and / or ethyl acetate.