Process of a quaternary ammonium salt
The present invention relates to a novel process for preparing quaternary ammonium salt derivatives.
1. A process for preparing a quaternary ammonium salt of formula (4):
wherein
X is halogen atom, C 1-6 alkylsulfonyloxy group, or C 6-10 arylsulfonyloxy group, and X − is a counteranion thereof,
Y is a substituent of the following formula (2a) or (2b):
wherein R 1 is independently methylene or oxygen atom; R 2 is independently C 1-6 alkyl group, C 1-6 alkoxy group, or hydroxy group; m and n are independently 0, 1, 2, or 3; and p is 1 or 2, and
Z is ═N—R 3 or ═CH—R 4 wherein R 3 is C 1-6 alkyl group, C 3-7 cycloalkyl group, C 5-7 cycloalkenyl group, C 6-10 aryl group, or 5- to 10-membered monocyclic or bicyclic heteroaryl group; R 4 is C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylthio group, C 3-7 cycloalkyl group, C 3-7 cycloalkyloxy group, C 3-7 cycloalkylthio group, C 5-7 cycloalkenyl group, C 5-7 cycloalkenyloxy group, C 5-7 cycloalkenylthio group, C 6-10 aryl group, C 6-10 aryloxy group, C 6-10 arylthio group, 5- to 10-membered monocyclic or bicyclic heteroaryl group, 5- to 10-membered monocyclic or bicyclic heteroaryloxy group, or 5- to 10-membered monocyclic or bicyclic heteroarylthio group,
comprising reacting a compound of formula (1):
wherein X is independently selected from the above-defined ones, and Y is as defined above,
with 1.8 to 15 mole of a compound of formula (3):
wherein Z is as defined above, per one mole of the compound of formula (1) to prepare the quaternary ammonium salt of formula (4).
2. The process of claim 1 wherein the reaction of Compound (1) with Compound (3) includes the following steps (i) and (ii):
step (i): reacting Compound (1) with 0.1 to 1.0 mole of Compound (3) per one mole of Compound (1), and then
step (ii): adding the rest of Compound (3) to the reaction mixture so that the total amount of Compound (3) can be 1.8 to 15 mole per one mole of Compound (1), and continuing the reaction.
3. The process of claim 1 wherein the reaction of Compound (1) with Compound (3) includes the following steps (i) and (ii):
step (i): reacting 0.1 to 1.0 mole of Compound (1) with 0.1 to 1.0 mole of Compound (3) per one mole of the total amount of Compound (1), and then
step (ii): adding the rest of Compound (1) and the rest of Compound (3) to the reaction mixture so that the total amount of Compound (3) can be 1.8 to 15 mole per one mole of the total amount of Compound (1), and continuing the reaction.
4. The process of claim 2 wherein the reaction is carried out in the presence of 0.1 to 1.0 mole of solid inorganic base per one mole of the total amount of Compound (1).
5. The process of claim 4 wherein the solid inorganic base is potassium carbonate.
6. The process of claim 4 wherein the amount of an solid inorganic base is 0.1 to 0.3 mole per one mole of the total amount of Compound (1).
7. The process of claim 2 wherein the amount of Compound (3) added in step (i) is 0.1 to 0.5 mole per one mole of the total amount of Compound (1).
8. The process of claim 2 wherein the total amount of Compound (3) in step (ii) is 1.8 to 5 mole per one mole of Compound (1).
9. The process of claim 1 wherein X is independently C 1-6 alkylsulfonyloxy group, or C 6-10 arylsulfonyloxy group.
10. The process of claim 9 wherein X is methanesulfonyloxy group.
11. The process of claim 1 wherein Y is the substituent of formula (2a).
12. The process of claim 11 wherein m is 2 and n is 0.
13. The process of claim 1 wherein Z is ═N—R 3 .
14. The process of claim 13 wherein R 3 is 5- to 10-membered monocyclic or bicyclic heteroaryl group.
15. The process of claim 14 wherein R 3 is 1,2-benzisothiazol-3-yl.
16. A process for preparing a quaternary ammonium salt of formula (4a):
comprising reacting a compound of formula (1a):
with 1.8 to 15 mole of a compound of formula (3a):
per one mole of the compound of formula (1a) to prepare the quaternary ammonium salt of formula (4a).
17. The process of claim 16 wherein the compound of formula (1a) is