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US 2004/0106788 A1Published application
Highly enantiomerically pure lactam-substituted propanoic acid derivatives and methods of making and using same
AssigneeEastman Chemical Company
InventorsNeil Warren Boaz, Sheryl Davis Debenham
Life of this patent
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Abstract
The present invention relates to highly enantiomerically pure lactam-substituted propanoic acid derivatives and methods of making and using therefor. The invention involves a multi-step synthesis to produce the lactam compounds. In one step of the reaction sequence, asymmetric hydrogenation of a lactam-enamide was performed to produce an intermediate that can ultimately be converted to a series of pharmaceutical compounds. The invention also contemplates the in situ synthesis of an intermediate of the multi-step synthesis, which provides economic advantages to the overall synthesis of the lactam compounds.
Claims50
A compound having the formula VII
- 14
- wherein R1, R2, and R3 are, independently, hydrogen, a substituted or unsubstituted, branched or straight chain C1 to C20 alkyl group;
- a substituted or unsubstituted C3 to C8 cycloalkyl group;
- a substituted or unsubstituted C6 to C20 aryl group;
- or substituted or unsubstituted C4 to C20 heteroaryl group having at least one heteroatom,
- n is from 0 to 5, and
- the stereochemistry at carbon a is substantially R or S.
4 more elements
A compound having the formula XI
- 17
- wherein R1, R3, and R4 are, independently, hydrogen, a substituted or unsubstituted, branched or straight chain C1 to C20 alkyl group;
- a substituted or unsubstituted C3 to C8 cycloalkyl group;
- a substituted or unsubstituted C6 to C20 aryl group;
- or substituted or unsubstituted C4 to C20 heteroaryl group, and
- n is from 0 to 5.
3 more elements
A method for producing a compound having the formula II,
- 18
- wherein R1 is hydrogen, substituted or unsubstituted, branched or straight chain C1 to C20 alkyl;
- substituted or unsubstituted C3 to C8 cycloalkyl;
- substituted or unsubstituted C6 to C20 aryl;
- or substituted or unsubstituted C4 to C20 heteroaryl, and
- n is from 0 to 5,
- comprising reacting a compound having the formula I
- 19
- with glyoxylic acid.
6 more elements
A method for producing the compound having the formula III,
- 20
- wherein R1, R3, and R4 are, independently, a substituted or unsubstituted, branched or straight chain C1 to C20 alkyl group;
- a substituted or unsubstituted C3 to C8 cycloalkyl group;
- a substituted or unsubstituted C6 to C20 aryl group;
- or a substituted or unsubstituted C4 to C20 heteroaryl group, wherein R1 can also be hydrogen, and
- n is from 0 to 5,
- comprising reacting the compound having formula II
- 21
- with an alcohol comprising an alkyl alcohol, an aryl alcohol, or a heteroaryl alcohol, wherein the alkyl alcohol is substituted or unsubstituted, branched or straight chain C1 to C20 alkyl or substituted or unsubstituted C3 to C8 cycloalkyl;
- the aryl alcohol is substituted or unsubstituted C6 to C20 aryl;
- and the heteroaryl alcohol is substituted or unsubstituted C4 to C20 heteroaryl, wherein the heteroatom is oxygen, nitrogen, or sulfur.
8 more elements
A compound having the formula V
- 22
- wherein R1 and R3 are, independently, substituted or unsubstituted, branched or straight chain C1 to C20 alkyl;
- substituted or unsubstituted C3 to C8 cycloalkyl;
- substituted or unsubstituted C6 to C20 aryl;
- or substituted or unsubstituted C4 to C20 heteroaryl, wherein R1 can also be hydrogen,
- R6 is substituted or unsubstituted, branched or straight chain C1 to C20 alkyl or substituted or unsubstituted C3 to C8 cycloalkyl, and
- n is from 0 to 5.
4 more elements
A method of producing a compound having the formula IV,
- 24
- wherein R1 and R3 are, independently, substituted or unsubstituted, branched or straight chain C1 to C20 alkyl;
- substituted or unsubstituted C3 to C8 cycloalkyl;
- substituted or unsubstituted C6 to C20 aryl;
- or substituted or unsubstituted C4 to C20 heteroaryl, wherein R1 can also be hydrogen,
- X is fluoride, chloride, bromide, or iodide, and
- n is from 0 to 5,
- comprising reacting a compound having the formula III
- 25
- wherein R1, R3, and R4 are, independently, a substituted or unsubstituted, branched or straight chain C1 to C20 alkyl group;
- a substituted or unsubstituted C3 to C8 cycloalkyl group;
- a substituted or unsubstituted C6 to C20 aryl group;
- or a substituted or unsubstituted C4 to C20 heteroaryl group, wherein R1 can also be hydrogen, and
- n is from 0 to 5,
- with a compound having the formula PX3, wherein X is fluoro, chloro, bromo, or iodo.
12 more elements
A compound having the formula VI
- 26
- wherein R1, R2, and R3 are, independently, hydrogen, substituted or unsubstituted, branched or straight chain C1 to C20 alkyl;
- substituted or unsubstituted C3 to C8 cycloalkyl;
- substituted or unsubstituted C6 to C20 aryl;
- or substituted or unsubstituted C4 to C20 heteroaryl, and
- n is from 0 to 5.
3 more elements
A method for producing a compound having the formula VIII
- 29
- wherein R1 and R2 are, independently, hydrogen, substituted or unsubstituted, branched or straight chain C1 to C20 alkyl;
- substituted or unsubstituted C3 to C8 cycloalkyl;
- substituted or unsubstituted C6 to C20 aryl;
- or substituted or unsubstituted C4 to C20 heteroaryl,
- n is from 0 to 5, and
- the stereochemistry at carbon a is substantially R or S,
- comprising reacting a compound having the formula VII
- 30
- wherein R3 is substituted or unsubstituted, branched or straight chain C1 to C20 alkyl;
- substituted or unsubstituted C3 to C8 cycloalkyl;
- substituted or unsubstituted C6 to C20 aryl;
- or substituted or unsubstituted C4 to C20 heteroaryl,
- with NH4OH.
11 more elements
Dependencies are inferred from the claim text.