Improved Method for the Synthesis of 2-Methyl-2-Aryloxypropanoic Acid Derivatives

Abstract

An improved method for the formation of 2-methyl-2-aryloxypropanoic acid derivatives, an important class of compounds for the potential treatment of type II diabetes, is reported. This method offers several advantages over the existing chemistry for this transformation.

2-methyl-2-aryloxypropanoic acid - PPAR agonist - alkylation - fibric acid

References

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The alkylation of one of our compounds using conditions reported by Bargellini was monitored by reaction calorimetry with a Metler Toledo RC1 unit. The total heat generated during the addition (1 h addition time) of the 1,1,1-trichloro-2-methyl-2-propanol was measured at 2180 kJ/kg. The average heat output rate for the duration of the addition was measured at 550 W/kg. Based on the reaction calorimetry, an adiabatic temperature rise of 58 °C was calculated.

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We thank Prof. Barry Trost, Stanford University, for first suggesting this reagent to us.

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The alkylation of the compound noted in ref. [6] with 2-bromo-2-methylpropanoic acid was monitored by reaction calorimetry with a Metler Toledo RC1 unit. The total heat generated during the addition (1 h addition time) of the 2-bromo-2-methylpropanoic acid was measured at 669 kJ/kg. The average heat output rate for the duration of the addition was measured at 141 W/kg. Based on the reaction calorimetry, an adiabatic temperature rise of 35 °C was calculated.

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