Method for preparation of Montelukast acid in ionic liquid medium
View Patent ↗The present invention relates to a method for preparing Montelukast acid or its sodium salt by reacting a thiol compound with a Montelukast intermediate in the presence of a base in a medium comprising an ionic liquid compound. In accordance with the inventive method, highly pure Montelukast acid or its sodium salt, which is advantageously used as a raw material in the preparation of Montelukast, a leukotriene antagonist, can be easily prepared in a high yield.
1. A method for preparing Montelukast acid of formula 1 or the sodium salt thereof, comprising
coupling a thiol compound of formula 2 with a Montelukast intermediate of formula 3 in the presence of a base in a medium comprising an ionic compound selected from the group consisting of 1-ethyl-3-methylimidazolium bromide, and N-butyl-N-methylpyrrolidium hexafluorophosphate to give the Montelukast acid of formula 1; and
optionally reacting the obtained Montelukast acid with NaOH, NaOCH 3 or sodium butoxide to give Montelukast sodium salt;
wherein R 1 , is hydrogen, methyl, or ethyl; and
L-O is a leaving group.
2. The method of claim 1 , wherein L is selected from the group consisting of methanesulfonyl, p-toluenesulfonyl, dimethylphosphoryl, diethylphosphoryl and diphenylsphosphoryl.
3. The method of claim 2 , wherein L is diphenylsphosphoryl.
4. The method of claim 1 , wherein the ionic liquid compound is employed in an amount ranging from 0.1 to 100 times the weight of the compound of formula 3.
5. The method of claim 1 , wherein the base is selected from the group consisting of potassium t-botoxide, sodium t-botoxide, NaH, NaOH, and KOH.
6. The method of claim 5 , wherein the base is potassium t-botoxide.