Ethyl benzoylformate → ethyl 2-cyclohexyl-2-hydroxy-2-phenylacetate
Reaction equation
[C:1]([C:9]([O:11][CH2:12][CH3:13])=[O:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:14]1([Mg]Br)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1>>[CH:2]1([C:1]([OH:8])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1Participants
Procedure
According to JP-A-11-193271, ethyl benzoylformate and cyclohexylmagnesium bromide are condensed to give ethyl 2-cyclohexyl-2-hydroxy-2-phenylacetate, which is hydrolyzed to give 2-cyclohexyl-2-hydroxy-2-phenylacetic acid. In this condensation reaction, diethyl ether having a boiling point of 35° C. is used in an amount of about 12-fold volume relative to ethyl benzoylformate, manipulation of dangerous reaction using the boiling point of diethyl ether is required and the yield is as low as 53.3%. In an attempt to improve this method into an industrially safe one, the present inventors used tetrahydrofuran instead of diethyl ether as a solvent and reproduced the reaction. As a result, there occurred reduction due to Grignard reagent to produce ethyl mandelate as a by-product, as well as addition of the Grignard reagent to ester bond. The proportion of the starting material that became a by-product was 42% and the yield of the objective product was as low as 58%. After hydrolysis of the obtained crude ethyl 2-cyclohexyl-2-hydroxy-2-phenylacetate, it was subjected to recrystallization and the like to increase the purity but the yield from ethyl benzoylformate of 2-cyclohexyl-2-hydroxy-2-phenylacetic acid did not exceed 43%.
Workup
- customcondensed
Sources & evidence
- ORD record
- ord-98814373bdc14fddbc91cda57821f1b0
- Source dataset
- uspto-grants-2004_08
- Patent number
- US06777576B2
Reaction notes
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