Pramoxine hydrochloride synthesis

Yield:637-58-1 82.61%

Reaction Conditions:

with sodium hydride in tetrahydrofuran at 20; for 5 h;Reflux;

Steps:

1 Example 1

A 500 ml reaction flask was added with 23.2 g (0.1 mol) of the above intermediate.3-morpholine-1-propanol 17.42g (0.12 mol) and 115 g of tetrahydrofuran, with stirring turned on, slowly add 60% sodium hydride 4.8g (0.12 mol), temperature below 20°C, about 1~2 min after addition,The reaction was heated to reflux and monitored by TLC. After about 5 hours, the reaction was completed. The solution was concentrated under reduced pressure. 60 ml of water was added and the pH was adjusted to 1 to 2 with concentrated hydrochloric acid.Ethyl acetate (100 ml) was washed twice. The aqueous layer was adjusted to pH 11-12 with 40% sodium hydroxide, and the mixture was extracted twice with 120 ml of ethyl acetate.Combine the organic layers, dry an appropriate amount of anhydrous sodium sulfate, decolorize with 2g of charcoal, concentrate at 40°C without concentration, and dissolve with 80ml of methanol.Concentrated hydrochloric acid to adjust the pH 1~2, vacuum concentration to no more, add acetone 40ml dissolved, stirring crystallization, continue to cool to -10 ° C, stirring crystallization about 6 ~ 8 hours;The mixture was filtered with suction, washed with cold acetone, and dried at 45-50° C. for 6-8 hours to obtain 27.25 g of a white crystalline solid with a yield of 82.61%, a purity of 99.926%, and a maximum single impurity of 0.046%.

References:

CN107892677,2018,A Location in patent:Paragraph 0019; 0021