Process and intermediate compounds useful in the preparation of statins, particularly atorvastatin
There is provided a process for the preparation of a compound of formula (7) or salts thereof: wherein R 1 represents a hydrogen or a hydrocarbyl group, R 2 represents a hydrogen or substituent group, R 3 represents a hydrogen or a hydrocarbyl group, and X represents a hydrogen or substituent group which comprises a) cyanating a compound of formula (1): wherein Y represents a halo group, preferably CI or Br; P 1 represents hydrogen or a protecting group, and W represents =0 or —OP 2 , in which P 2 represents hydrogen or a protecting group, to give a compound of formula (2): b) reducing the compound of formula (2) to give a compound of formula (3): coupling the compound of formula (3) with a compound of formula (4): to give a compound of formula (5): when W represents —OP 2 , deprotecting and then oxidising the compound of formula (5) to give a compound of formula (6): and e) subjecting the compound of formula (5) when W represents ═O, or compound of formula (6) to ring-opening, and removal of any remaining protecting groups, to give a compound of formula (7) or salts thereof
1. A compound of formula (5):
wherein
R 1 represents an alkyl group;
R 2 represents an aryl group;
R 3 represents an aryl group;
X represents a group of formula —COZ, wherein Z represents —OR 4 , in which R 4 represents an alkyl, or —NR 5 R 6 , wherein R 5 and R 6 each independently represent H, alkyl, or aryl;
P 1 represents hydrogen or a protecting group; and
W represents —OP 2 , in which P 2 represents hydrogen or a protecting group.
2. The compound of claim 1 , wherein R 1 represents a C 1-6 alkyl group.
3. The compound of claim 1 , wherein R 1 represents an isopropyl group.
4. The compound of claim 1 , wherein R 2 represents a phenyl group.
5. The compound of claim 1 , wherein R 3 represents a 4-fluorophenyl group.
6. The compound of claim 1 , wherein Z represents -OR 4 , in which R 4 represents an alkyl.
7. The compound of claim 1 , wherein Z represents -OR 4 , in which R 4 represents a methyl or ethyl group.
8. The compound of claim 1 , wherein Z represents -NR 5 R 6 , wherein R 5 and R 6 each independently represent H, alkyl, or aryl.
9. The compound of claim 1 , wherein Z represents -NR 5 R 6 , wherein R 5 is H and R 6 is phenyl.
10. The compound of claim 1 , wherein R 1 represents a C 1-6 alkyl group; and R 2 represents a phenyl group.
11. The compound of claim 1 , wherein R 1 represents a C 1-6 alkyl group; R 2 represents a phenyl group; and R 3 represents a 4-fluorophenyl group.
12. The compound of claim 1 , wherein R 1 represents a C 1-6 alkyl group; R 2 represents a phenyl group; R 3 represents a 4-fluorophenyl group; and Z represents -OR 4 , in which R 4 represents a methyl or ethyl group.
13. The compound of claim 1 , wherein R 1 represents a C 1-6 alkyl group; R 2 represents a phenyl group; R 3 represents a 4-fluorophenyl group; and Z represents -NR 5 R 6 , wherein R 5 is H and R 6 is phenyl.