Back to results
US 6,410,794 B1Granted
Process for preparation of pharmaceutically desired chiral tetralone from tetralones
AssigneeUop LLC
InventorsHerman A. Zinnen, Mark J. Gattuso
Life of this patent
Estimating the term…
Abstract
Improved processes for preparation of tetralones in high enantiomeric purity centers on resolution using simulated moving bed chromatography of a racemic tetralone derivative. Resolution is effected with high enantiomeric purity, and subsequent reactions of the desired tetralone derivative enantiomer performed with high optical specificity to maintain enantiomeric purity. The undesired enantiomer may be racemized and recycled to the resolution phase to avoid loss.
Claims22
In a process for preparation of compounds of formula III
- by selectively converting a carbonyl protected compound of formula V to III
- where R1 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethyl, and alkoxy having from 1 to 3 carbon atoms, where X and Y are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, and alkoxy having from 1 to 3 carbon atoms, with at least one of X or Y being other than hydrogen, and •˜P˜• is a carbonyl protecting group, the improvement comprising the selective preparation of III of at least 95% enantiomeric purity by:
- a) resolving racemic V, in a resolution stage, by simulated moving bed chromatography using a chiral adsorbent to afford a first enantiomer of V in at least 95% enantiomeric purity and a second enantiomer of V;
- b) selectively converting the first enantiomer of V to compound III;
- and
- c) racemizing the second enantiomer of V to racemic V and recycling the racemic V to the resolution stage.
3 more elements
In a process for preparation of compounds of formula III
- by selectively converting a compound of formula VI or VII to III
- where R1 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethyl, and alkoxy having from 1 to 3 carbon atoms, where X and Y are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, and alkoxy having from 1 to 3 carbon atoms, with at least one of X or Y being other than hydrogen, and P′ is a hydroxyl protecting group, the improvement comprising the selective preparation of III of at least 95% enantiomeric purity by:
- a) resolving racemic VI or VII in a resolution stage by simulated moving bed chromatography using a chiral adsorbent to afford a first enantiomer of VI or VII in at least 95% enantiomeric purity and a second enantiomer of VI or VII;
- b) selectively converting the first enantiomer of VI or VII to compound III;
- and
- c) racemizing the second enantiomer of VI or VII to racemic VI or VII and recycling the racemic VI or VII to the resolution stage.
3 more elements
In a process for preparation of compounds of formula III
- by selectively converting a compound of formula VIII or IX to III
- where R1 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethyl, and alkoxy having from 1 to 3 carbon atoms, where X and Y are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, trifluoromethyl, cyano, and alkoxy having from 1 to 3 carbon atoms, with at least one of X or Y being other than hydrogen, the improvement comprising the selective preparation of III of at least 95% enantiomeric purity by:
- a) resolving racemic VIII or IX in a resolution stage by simulated moving bed chromatography using a chiral adsorbent to afford a first enantiomer of VIII or IX in at least 95% enantiomeric purity and a second enantiomer of VIII or IX;
- b) selectively converting the first enantiomer of VIII or IX to compound III;
- and
- c) racemizing the second enantiomer of VIII or IX to racemic VIII or IX and recycling the racemic VIII or IX to the resolution stage.
3 more elements
Dependencies are inferred from the claim text.