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US 2006/0040898 A1Published application
Novel boronate esters
AssigneeBiocon Limited
InventorsTom Puthiaparampil, Sumithra Srinath, Madhavan Sridharan, Sambasivam Ganesh
Life of this patent
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Abstract
The present invention relates to optically active boronate derivatives which are useful as intermediates for the synthesis of HMG-CoA enzyme inhibitors such as atorvastatin, cerivastatin, rosuvastatin, pitavastatin, and fluvastatin.
Claims23
A compound of formula Ia:
- wherein:
- Ar is an unsubstituted or substituted ring selected from C6-10 monocyclic or bicyclic aryl or a 5-10 membered monocyclic or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl;
- R4 is O, OH, CN, LG, or halogen, wherein LG is a suitable leaving group;
- and
- represents a single or double bond.
3 more elements
A process for the manufacture of a compound of formula II:
- wherein:
- Ar is an unsubstituted or substituted ring selected from C6-10 monocyclic or bicyclic aryl or a 5-10 membered monocyclic or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- which method comprises the steps of:
- (a) reacting a compound of formula III:
- wherein:
- G is a suitable hydroxyl protecting group, with the anion of a suitable acetate to give a compound of formula IV:
- where:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- (b) subjecting the compound of formula IV to reduction to give a compound of formula V:
- wherein:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- (c) reacting the compound of formula V with ArB(OH)2 to give a compound of formula VI:
- wherein:
- Ar is an unsubstituted or substituted ring selected from C6-10 monocyclic or bicyclic aryl or a 5-10 membered monocyclic or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- and
- (f) deprotection of the compound of formula VI to give a compound of formula II.
22 more elements
A method for preparing a compound of formula IIb:
- wherein:
- Ar is an unsubstituted or substituted ring selected from C6-10 monocyclic or bicyclic aryl or a 5-10 membered monocyclic or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- and
- R3 is a straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- which comprises the steps of:
- (a) reacting a compound of formula III-1:
- wherein:
- G is a suitable hydroxyl protecting group,
- with the anion of a suitable acetate to give a compound of formula IV-1:
- wherein:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- (b) reducing said compound of formula IV-1 to give a compound of formula V-1:
- where:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- (c) reacting the compound of formula V-1 with ArB(OH)2 to give a compound of formula VI-1:
- where:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- and
- (d) deprotection of the compound of formula VI-1 to give a compound of formula IIb.
22 more elements
A method for method for preparing a compound of formula II-1:
- wherein:
- Ar is an unsubstituted or substituted ring selected from C6-10 monocyclic or bicyclic aryl or a 5-10 membered monocyclic or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- and
- R3 is a straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- which comprises the steps of:
- (a) reacting a compound of formula III-1:
- wherein:
- G is a suitable hydroxyl protecting group,
- with the anion of a suitable acetate to give a compound of formula IV-1:
- wherein:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- (b) reducing said compound of formula IV-1 to give a compound of formula V-3:
- where:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- (c) reacting the compound of formula V-3 with ArB(OH)2 to give a compound of formula VI-3:
- where:
- G is a suitable hydroxyl protecting group;
- and
- R3 is straight or branched C1-8 alkyl, C6-10 monocyclic or bicyclic aryl, or C6-10 monocyclic or bicyclic aryl(C1-6)alkyl,
- and
- (d) deprotection of the compound of formula VI-3 to give a compound of formula II-1.
22 more elements
Dependencies are inferred from the claim text.