Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates
View Patent ↗Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively wherein, R 1 and R 2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR 3 R 4 , OR 5 , or SR 5 , where R 3 and R 4 are individually selected from acyl or sulfonyl, and where R 5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.
1. A method of preparing
wherein
Y is selected from the group consisting of
and
Ar is selected from the group consisting of
provided that when Y is
then Ar is
or when Y is
then Ar is
or when Y is
then Ar is
comprising
(i) alkylating 1,3,2-dioxathiane 2,2-dioxide having the formula
with
in the presence of base selected from potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, potassium hydroxide, sodium hydroxide, magnesium hydroxide or calcium hydroxide, to form the corresponding alkylation compound of the formula
wherein Q is potassium, sodium, magnesium or calcium,
(ii) hydrolyzing the alkylation compound of step (i) with aqueous acid to obtain the corresponding hydroxyl compound of formula
wherein Y is selected from the group consisting of
(iii) converting the compound of formula
of step (ii) to the corresponding alkylating agent compound of formula
wherein LG is an aryl sulfonate or alkyl sulfonate, and
(iv) alkylating the compound of formula
of step (iii) with the compound of formula
wherein Ar is selected from the group consisting of
in the presence of base selected from potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, potassium hydroxide, sodium hydroxide, magnesium hydroxide or calcium hydroxide,
provided that when Y is
then Ar is
or when Y is
then Ar is
or when Y is
then Ar is
2. The process of claim 1 wherein the base of steps (i) and (iv) is potassium carbonate.
3. The process of claim 1 wherein LG is methylsulfonate.
4. The process of claim 1 wherein Y is
and Ar is
5. The process of claim 1 wherein Y is
and Ar is
6. The process of claim 1 wherein Y is
and Ar is