Process and intermediate compounds useful in the preparation of statins, particularly rosuvastatin
Provided are a compound of formula (5) and a process for its preparation wherein: R 1 represents an alkyl group; R 2 represents an aryl group; R 3 represents a protecting group or an alkyl group; R 4 represents a protecting group or a SO 2 R 5 group where R 5 is an alkyl group; R 6 represents (PR 7 R 8 ) + X − or P(═O)R 7 R 8 in which X is an anion and R 7 and R 8 each independently is an alkyl, aryl, alkoxy, or aryloxy group; P 1 represents hydrogen or a protecting group; and W represents ═O or OP 2 , in which P 2 represents hydrogen or a protecting group.
1. A process for the preparation of a compound of formula (5)
comprising coupling a compound of formula (3)
with a compound of formula (4)
wherein:
R 1 represents an alkyl group;
R 2 represents an aryl group;
R 3 represents a protecting group or an alkyl group;
R 4 represents a protecting group or a SO 2 R 5 group where R 5 is an alkyl group;
R 6 represents (PR 7 R 8 ) + X − or P(═O)R 7 R 8 in which X is an anion and R 7 and R 8 each independently is an alkyl, aryl, alkoxy, or aryloxy group;
P 1 represents hydrogen or a protecting group; and
W represents —OP 2 , in which P 2 represents hydrogen or a protecting group.
2. A compound of formula (5)
wherein:
R 1 represents an alkyl group;
R 2 represents an aryl group;
R 3 represents hydrogen, a protecting group, or an alkyl group;
R 4 represents a protecting group or a SO 2 R 5 group where R 5 is an alkyl group;
P 1 represents hydrogen or a protecting group; and
W represents —OP 2 , in which P 2 represents hydrogen or a protecting group.
3. The process of claim 1 , wherein each of R 7 and R 8 is a phenyl group.
4. The process of claim 1 , wherein R 1 represents a C 1-6 alkyl group.
5. The process of claim 4 , wherein R 1 represents an isopropyl group.
6. The process of claim 1 , wherein R 2 is 4-fluorophenyl group.
7. The process of claim 1 , wherein R 3 represents a C 1-6 alkyl group.
8. The process of claim 1 , wherein R 3 represents a methyl group.
9. The process of claim 1 , wherein R 5 is a C 1-6 alkyl group.
10. The process of claim 9 , wherein R 5 is a methyl group.
11. The process of claim 1 , wherein P 1 represents hydrogen or a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl.
12. The process of claim 1 , wherein P 2 represents a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl.
13. The compound of claim 2 , wherein R 1 represents a C 1-6 alkyl group.
14. The compound of claim 13 , wherein R 1 represents an isopropyl group.
15. The compound of claim 2 , wherein R 2 is 4-fluorophenyl group.
16. The compound of claim 2 , wherein R 3 represents a C 1-6 alkyl group.
17. The compound of claim 2 , wherein R 3 represents a methyl group.
18. The compound of claim 2 , wherein R 5 is a C 1-6 alkyl group.
19. The compound of claim 18 , wherein R 5 is a methyl group.
20. The compound of claim 2 , wherein P 1 represents hydrogen or a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl.
21. The compound of claim 2 , wherein P 2 represents a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl.