3'-Chloropropiophenone CAS 34841-35-5

3′-Chlorophenylpropanol, as an important intermediate in the synthesis of dapoxetine, plays a key role in the cost and quality of the entire drug. About the synthesis report of R-3′-chlorophenylpropanol, mainly focus on taking 3′-chloropropiophenone as raw material, through reducing agent, synthesizes target product.

The target compound is synthesized by using tetrahydrofuran as a solvent and a spiro boron ester compound as a catalyst. The cost of this process solvent and catalyst is relatively high. With 95% ethanol as solvent and potassium borohydride as reducing agent, the cost is low. However, the synthesized product is a mixture, which needs to be split before the target product can be formed, and the final total yield is low, resulting in high cost. DMSO is used as solvent, and chiral catalysts are not common and have high cost. The post-processing is complicated and the energy consumption is large. Using ethylene glycol dimethyl ether as solvent and sodium borohydride as reducing agent. The cost of the solvent is high, and the product is a mixture that needs to be split.

To sum up, in the synthesis technique of R-3′-chlorophenylpropanol, there are ubiquitous shortcomings such as high solvent and reducing agent cost, difficult aftertreatment, difficult control of reaction process, low selectivity, low chiral purity, etc. To sum up, the research on the synthesis process of R-3′-chlorophenylpropanol, the development of a production process with lower cost, convenient handling and better product quality, is of great significance to the synthesis of the above-mentioned drugs and the treatment of related diseases. Has a broad market prospect.

Adopt the technique of 3-chloropropiophenone to synthesize 3′-chlorophenylpropanol, the concrete steps are as follows:

1) Add 3′-chloropropiophenone and L-prolinol successively to 95% ethanol and stir;

2) Cool down after the reaction solution is completely dissolved;

3) Add potassium borohydride to the reaction solution in batches, and keep the temperature after adding;

4) After the reaction solution is heated to reflux for reaction, the reaction solution is concentrated under reduced pressure;

5) Add n-hexane to the reaction solution, heat, and then add activated carbon to decolorize by heat preservation;

6) Filter the reaction solution, rinse the filter cake with 500-700ml of n-hexane, and collect the filtrate;

7) The filtrate is crystallized and filtered, and the filter cake is rinsed once with 300-500ml of n-hexane, and dried in vacuum to obtain 3′-chlorophenylpropanol.

The method includes the steps:

1) Make 3-chloropropiophenone and 3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane The alkane reaction obtains the compound whose structure is shown in formula 5;

2) reacting the compound with the structure shown in formula 5 with the chiral auxiliary (S)-tert-butyl sulfinamide to generate the compound shown in the structure shown in formula 4;

3) reducing the compound of formula 4 to obtain the compound of formula 3; and

4) (S)-3-((3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)- 8-azabicyclo[3.2.1]octane-8-yl)-1-phenylpropylamine hydrochloride is treated with an alkaline solution to obtain the compound whose structure is shown in formula 2;