Piperidine derivatives and process for their production

1. A process of preparing a piperidine derivative compound of the formula:

wherein

R 1 is hydrogen or hydroxy;

R 2 is hydrogen;

or R 1 and R 2 taken together form a second bond between the carbon atoms bearing R 1 and R 2 ;

R 3 is —COOH or —COOR 4 ;

R 4 has 1 to 6 carbon atoms;

said process comprising:

providing a regioisomer of the following formula:

converting the regioisomer to the piperidine derivative compound with a piperidine compound of the formula:

2. A process according to claim 1 , wherein said providing comprises:

acylating a starting compound of the formula:

wherein

R 5 is OR 6 , —N(R 6 ) 2 , and —SR 6 , and

R 6 is an alkyl with 1 to 6 carbons, with a compound of the formula:

wherein

X is a halogen, under conditions effective to produce a first mixture of regioisomers of the formula:

hydrolyzing the first mixture of regioisomers under conditions effective to form a second mixture of a regioisomers of the formula:

recovering from the second mixture of regioisomers the regioisomer of the formula:

3. A process according to claim 2 , wherein said recovering comprises:

crystallizing from the second mixture of regioisomers a regioisomer salt of the formula:

wherein X + is a Lewis Acid;

isolating the regioisomer salt; and

converting the regioisomer salt to the regioisomer of the formula:

4. A process according to claim 3 , wherein X + is an alkali metal salt or an ammonium salt of the form NR 7 R 8 R 9 wherein R 7 , R 8 , and R 9 are individually hydrogen or a straight or branched alkyl of 1 to 6 carbon atoms, or an alkyl substituted at any position with a phenyl ring or a substituted phenyl ring.

5. A process according to claim 2 , wherein said acylating is carried out by a Friedel-Crafts reaction using AlCl 3 catalyst.

6. A process according to claim 1 , further comprising:

reducing the piperidine derivative under conditions effective to form a hydroxylated piperidine derivative of the formula:

7. A process according to claim 6 , wherein the hydroxylated piperidine derivative has the formula:

8. A process according to claim 1 , wherein said converting comprises:

halogenating the regioisomer of the following formula:

under conditions effective to form a first intermediate compound of the formula:

wherein X is a halogen and

reacting the first intermediate compound with a piperidine compound of the formula:

under conditions effective to form the piperidine derivative of the following formula:

9. A process according to claim 1 , wherein said converting comprises:

reacting the regioisomer of the following formula:

with a piperidine compound of the formula:

under conditions effective to form the piperidine derivative of the formula: