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US 10,421,712 B2Granted
Difluoroalkylcyclopropyl amino acids and esters, and syntheses thereof
AssigneeAbbVie Inc.
InventorsKirill A. Lukin, Jianzhang Mei, David R. Hill, Michael J. Abrahamson
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Abstract
The invention provides methods of synthesizing compounds in an asymmetric or enantioenriched fashion, wherein the compounds are useful intermediates in the synthesis of viral protease inhibitors.
Claims18
A method, comprising:
- contacting, in an eighth solvent, a compound of formula I with a fifth base, thereby forming a compound of formula J;
- wherein:
- formula I is
- formula J is
- or a salt thereof;
- and
- R is ethyl or n-propyl.
4 more elements
A method, comprising:
- subjecting a compound of formula F to simulated moving bed chromatography, thereby obtaining the enantioenriched compound of formula I;
- wherein
- formula F is
- formula I is
- and
- R is alkyl.
3 more elements
A method according to the following scheme:
- wherein R is ethyl or n-propyl.
A method, comprising:
- selectively hydrolyzing with a first enzyme the 2S-enantiomer of a compound of formula D, thereby forming a fourteenth product mixture;
- separating from the fourteenth product mixture an enantioenriched amount of the 2R-enantiomer of a compound of formula D, thereby forming a fifteenth product mixture comprising an enantioenriched compound of formula G;
- regioselectively hydrolyzing with a second enzyme the compound of formula G, thereby forming a sixteenth product mixture comprising a compound of formula H,
- wherein
- formula D is
- formula G is
- formula H is
- or a salt thereof;
- and
- R is ethyl or n-propyl;
- the first enzyme is Mucor miehei lipase (RML enzyme);
- and
- the second enzyme is Bacillus subtilis esterase (yvaK enzyme).
10 more elements
A method according to the following scheme:
- wherein R is ethyl or n-propyl.
A method, comprising:
- heating a compound of formula C and trimethylsulfoxonium iodide in the presence of a second base and a second solvent at a fourth temperature for a fourth period of time, thereby forming a third product mixture comprising a compound of formula D,
- wherein
- formula C is
- formula D is
- and
- R is ethyl or n-propyl.
3 more elements
Dependencies are inferred from the claim text.