Process for the synthesis of (R)-1-(3,5-bis(trifluoromethyl)-phenyl)ethan-1-ol by asymmetric transfer hydrogenation
AssigneeMerck & Co., Inc.
InventorsPaul Devine, Hansen Karl
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Abstract
The present invention is concerned with novel processes for the preparation of (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol. This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.
Claims20
A process for the preparation of a compound of the formula:
- 16
- which comprises:
- treating a compound of the formula:
- 17
- with a rhodium or a ruthenium catalyst and a ligand in the presence of an alcohol;
- to give the compound of the formula:
- 18
A process for the preparation of (R)-1-(3,5-bis(trifluoro-methyl)phenyl)ethan-1-ol which comprises:
- treating 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one with bis((pentamethylcyclopentadienyl)rhodium chloride) and (S,R)-cis-1-amino-2-hydroxy-indane in the presence of isopropanol,
- to give (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol.
A process for the preparation of (R)-1-(3,5-bis(trifluoro-methyl)phenyl)ethan-1-ol which comprises:
- treating 1-(3 ,5-bis(trifluoromethyl)phenyl)ethan-1-one with bis((4-isopropyl-toluenyl)ruthenium chloride) and (S,R)-cis-1-amino-2-hydroxy-indane in the presence of isopropanol,
- to give (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol.
A compound which is:
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- wherein Cp* is pentamethylcyclopentadienyl.
A compound which is:
- 20
- wherein Cym* is 4-isopropyl-toluene.
A compound which is:
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A process for the purification of (R)-1-(3,5-bis(trifluoro-methyl)phenyl)ethan-1-ol which comprises:
- contacting (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol with 1,4-diazabicyclo[2.2.2]octane in an organic solvent to form bis-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol) 1,4-diazabicyclo[2.2.2]octane;
- recovering the bis-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol) 1,4-diazabicyclo[2.2.2]octane;
- and dissociating the 1,4-diazabicyclo[2.2.2]octane from the bis-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol) 1,4-diazabicyclo[2.2.2]octane to give (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol.
Dependencies are inferred from the claim text.