3-O-tert-butyl 1-O-methyl 2-methylpropanedioate

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

Procedure: 9.91 Gram (95%, 56.9 mmol) of tert-butyl methyl malonate was dissolved in 120 mL of tetrahydrofuran (THF), and the resulting solution was added dropwise to a suspension containing 2.28 g (60 wt %, 56.9 mmol) of sodium hydride (NaH) and 120 mL of THF at 0° C. over 0.5 hours, followed by stirring for 0.5 hours. Thereafter, a solution containing 8.08 g (56.9 mmol) of methyl iodide (MeI) and 20 mL of TI-IF was added dropwise over 0.5 hours, and the resulting mixture was stirred at 0° C. for 0.5 hours and further stirred at 25° C. for 5 hours. After adding 200 of ethyl acetate, the organic layer was washed, in order, twice with saturated brine and twice with water, and dried over sodium sulfate, and the solvent was concentrated to obtain 13.0 g of 1-tert-butyl 3-methyl 2-methylmalonate as a colorless transparent oil. Subsequently, 45.9 g of an aqueous formalin solution was added to 13.0 g of the oil, and resulting mixture was cooled to 0° C. Furthermore, 7.81 g of potassium carbonate was added, and the mixture was stirred at 0° C. for 1 hour and further stirred at 25° C. for 3 hours. After adding 200 mL of ethyl acetate, the organic layer was washed, in order, three times with an aqueous saturated sodium hydrogensulfite solution and twice with water, and dried over sodium sulfate. The solvent was concentrated, and the residue was dissolved in 50 mL of pyridine. The resulting solution was cooled to 0° C., and 21.7 g of p-toluenesulfonyl chloride was added thereto. The obtained mixture was stirred at 0° C. for 2 hours and then stirred at 60° C. for 4 hours. After adding 200 mL of ethyl acetate, the organic layer was washed, in order, three times with an aqueous saturated ammonium chloride solution and twice with water, and dried over sodium sulfate. The residue was purified by column chromatography (SiO2, hexane/ethyl acetate=4/1) to obtain 15.8 g of the objective Compound (I-31) as a colorless transparent oil. the resulting solution was added dropwise to a suspension was added dropwise over 0.5 hours the resulting mixture was stirred at 0° C. for 0.5 hours further stirred at 25° C. for 5 hours the organic layer was washed, in order, twice with saturated brine and twice with water dried over sodium sulfate the solvent was concentrated