2,2-dimethyl-3-[(2-methylpropan-2-yl)oxy]-3-oxopropanoic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2,2-dimethylmalonic acid mono-t-butyl ester (10 g), 2,2-dimethyl-1-propanol [CAS No. 75-84-3] (5.15 g), DMAP (1.3 g), and dichloromethane (100 mL), WSC (12.2 g) was added with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 2 days. TBME and water were added to the mixture, and the resulting mixture was extracted. The organic layer was sequentially washed with water and saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain 2,2-dimethylmalonic acid t-butyl ester(2,2-dimethylpropyl)ester (12 g). cooling the resulting mixture was stirred at room temperature for 2 days the resulting mixture was extracted The organic layer was sequentially washed with water and saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate The desiccant was filtered off the filtrate obtained was concentrated under reduced pressure The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2,2-dimethylmalonic acid mono-t-butyl ester [CAS No. 143688-40-8] (800 mg), DMAP (104 mg), and dichloromethane (8 mL), cyclohexanol (0.494 mL) and WSC (976 mg) were sequentially added at 0° C. The resulting mixture was stirred overnight at room temperature, and TBME (50 mL) was added thereto. The resulting mixture was sequentially washed with water (30 mL) and saturated aqueous sodium chloride solution (30 mL), and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain the captioned compound (817 mg). The resulting mixture was sequentially washed with water (30 mL) and saturated aqueous sodium chloride solution (30 mL) dried over anhydrous magnesium sulfate The resulting mixture was filtered the filtrate obtained was concentrated under reduced pressure The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of [1-amino-1-[4-({(5-chloromethoxy-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}amino)phenyl]methylidene]carbamic acid 2,2-dimethylpropyl ester (170 mg), 2,2-dimethylmalonic acid mono-t-butyl ester [CAS No. 143688-40-8] (490 mg), sodium iodide (390 mg), potassium hydrogen carbonate (182 mg), and DMA (25 mL) was stirred at 50° C. overnight. After cooling the mixture to room temperature, 1:1 mixture of water and saturated aqueous sodium chloride and ethyl acetate were added thereto, and the resulting mixture was extracted. The aqueous layer was reextracted with ethyl acetate twice. All the organic layers were combined, washed with water, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain a racemate of the captioned compound. were added the resulting mixture was extracted washed with water dried over anhydrous magnesium sulfate The desiccant was filtered off the filtrate obtained was concentrated under reduced pressure The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain a racemate of the captioned compound