The present invention relates to a process for preparing a pharmaceutical starting compound compound by hydrolyzing a compound of the general formula (II): Wherein R 1 is protected carboxy, R 2 is lower alkoxy or higher alkoxy, A 1 is an aromatic bivalent group, heterocyclic bivalent group or cyclo (lower) alkane bivalent group, and A 2 is an aromatic bivalent group, heterocyclic bivalent group or cyclo (lower) alkane bivalent group, with aqueous potassium hydroxide and by treating with hydrochloric acid.
1. A process for preparing a compound of the formula (III):
wherein R 2 is lower alkoxy or higher alkoxy,
R 4 is carboxy
A 1 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group, and
A 2 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group,
which comprises:
hydrolyzing a compound of the general formula (II):
wherein R 2 , A 1 and A 2 are each as defined above, and
R 1 is protected carboxy, with aqueous potassium hydroxide to give a compound of the general formula (I):
wherein R 2 , A 1 and A 2 are each as defined above, and
R 3 is a potassium salt of carboxy, and reacting this compound (I) with hydrochloric acid to obtain the compound (III).
2. A process of claim 1 , wherein
R 2 is lower alkoxy,
A 1 is an aromatic bivalent group or heterocyclic bivalent group, and
A 2 is an aromatic bivalent group or heterocyclic bivalent group.
3. A process of claim 2 , wherein
A 1 is an aromatic bivalent group, and
A 2 is an aromatic bivalent group.
4. A process of claim 3 , wherein
A 1 is phenylene, and
A 2 is phenylene.
5. A process for preparing a compound of the formula (I):
wherein R 2 is lower alkoxy or higher alkoxy,
R 3 is a potassium salt of carboxy,
A 1 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group, and
A 2 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group,
which comprises:
hydrolyzing a compound of the general formula (II):
wherein R 2 , A 1 and A 2 are each as defined above, and
R 1 is protected carboxy,
with aqueous potassium hydroxide to give the compound (I).
6. A process of claim 5 , wherein
R 2 is lower alkoxy,
A 1 is an aromatic bivalent group or heterocyclic bivalent group, and
A 2 is an aromatic bivalent group or heterocyclic bivalent group.
7. A process of claim 6 , wherein
A 1 is an aromatic bivalent group, and
A 2 is an aromatic bivalent group.
8. A process of claim 7 , wherein
A 1 is phenylene, and
A 2 is phenylene.
9. A process for preparing a compound of the formula (III):
wherein R 2 is lower alkoxy or higher alkoxy,
R 4 is carboxy
A 1 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group, and
A 2 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group,
which comprises:
reacting a compound of the general formula (I):
wherein R 2 , A 1 and A 2 are each as defined above, and
R 3 is a potassium salt of carboxy,
with hydrochloric acid to obtain the compound (III).
10. A process of claim 9 , wherein
R 2 is lower alkoxy,
A 1 is an aromatic bivalent group or heterocyclic bivalent group, and
A 2 is an aromatic bivalent group or heterocyclic bivalent group.
11. A process of claim 10 , wherein
A 1 is an aromatic bivalent group, and
A 2 is an aromatic bivalent group.
12. A process of claim 11 , wherein
A 1 is phenylene, and
A 2 is phenylene.
13. A process for preparing a compound of the formula (V):
wherein R 2 is lower alkoxy or higher alkoxy,
A 1 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group, and
A 2 is an aromatic bivalent group, heterocyclic bivalent group or cyclo(lower)alkane bivalent group, or salt thereof,
which comprises:
hydrolyzing a compound of the general formula (II):
wherein R 2 , A 1 and A 2 are each as defined above, and
R 1 is protected carboxy,
with aqueous potassium hydroxide to give a compound of the general formula (I):
wherein R 2 , A 1 and A 2 are each as defined above, and
R 3 is a potassium salt of carboxy,
and reacting this compound (I) with hydrochloric acid to give the compound of the general formula (III):
wherein R 2 A 1 and A 2 are each as defined above, and
R 4 is carboxy, and if necessary, converting the compound (III) into its reactive derivative at the carboxy group or a salt thereof in a conventional manner,
and reacting the compound (III) or its reactive derivative at the carboxy group or a salt thereof with the compound of the formula (IV):
or its reactive derivative at the amino group or a salt thereof to obtain the compound (V) or a salt thereof.
14. A process of claim 13 , wherein
R 2 is lower alkoxy,
A 1 is an aromatic bivalent group or heterocyclic bivalent group, and
A 2 is an aromatic bivalent group or heterocyclic bivalent group.
15. A process of claim 14 , wherein
A 1 is an aromatic bivalent group, and
A 2 is an aromatic bivalent group.
16. A process of claim 15 , wherein
A 1 is phenylene, and
A 2 is phenylene.
17. A process of claim 1 , wherein formula (III) is 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid.