tert-butyl 3-(4-methoxyphenyl)-2-methylpropanoate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven dried flask was charged with THF (40 mL) under nitrogen and cooled to −78° C. and 2M LDA in THF (7.19 mL, 14.38 mmol) was added dropwise followed by DMPU (8 mL, 5.75 mmol). Tert-butyl 3-(4-methoxyphenyl)-2-methylpropanoate (1.44 g, 5.75 mmol) was added by cannula in THF (4×5 mL), and the reaction was stirred at −78° C. for 1 hr. Methyl iodide (1.079 mL, 17.26 mmol) was added dropwise, and the reaction was stirred 30 minutes at −78° C. and then warmed to room temperature for 1 hr. The reaction was quenched with water (40 mL) and extracted with ethyl acetate (50 mL). The organic layer was washed with 1N HCl (2×30 mL) and brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (0 to 60% ethyl acetate/hexanes) afforded tert-butyl 3-(4-methoxyphenyl)-2,2-dimethylpropanoate. 1H NMR (CDCl3, 500 MHz) δ 7.07 (d, J=8.5 Hz, 2H), 6.79 (d, J=8.7 Hz, 2H), 3.78 (s, 3H), 2.76 (s, 2H), 1.43 (s, 9H), 1.11 (s, 6H). An oven dried flask was charged with THF (40 mL) under nitrogen the reaction was stirred 30 minutes at −78° C. warmed to room temperature for 1 hr The reaction was quenched with water (40 mL) extracted with ethyl acetate (50 mL) The organic layer was washed with 1N HCl (2×30 mL) and brine (2×30 mL) dried over sodium sulfate filtered concentrated Purification of the residue by flash chromatography on silica gel (0 to 60% ethyl acetate/hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven dried flask was charged with THF (40 mL) under nitrogen and cooled to −78° C. and 2M LDA in THF (7.62 mL, 15.23 mmol) was added dropwise followed by DMPU (8 mL, 6.09 mmol). Tert-butyl 3-(4-methoxyphenyl)propanoate (1.44 g, 6.09 mmol) was added by cannula in THF (4×5 mL), and the reaction was stirred at −78° C. for 1 hr. Methyl iodide (1.143 mL, 18.28 mmol) was added dropwise, and the reaction was stirred 30 minutes at −78° C. and then warmed to room temperature for 1 hr. The reaction was then quenched with water (40 mL) and extracted with ethyl acetate (50 mL). The organic layer was washed with 1N HCl (2×30 mL) and brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (0 to 60% ethyl acetate/hexanes) afforded of tert-butyl 3-(4-methoxyphenyl)-2-methylpropanoate. 1H NMR (CDCl3, 500 MHz) δ 7.09 (d, J=8.5 Hz, 2H), 6.81 (d, J=8.5 Hz, 2H), 3.78 (s, 3H), 2.89 (multiplet, 1H), 2.57 (multiplet, 2H), 1.38 (s, 9H), 1.10 (d, J=6.4 Hz, 3H). An oven dried flask was charged with THF (40 mL) under nitrogen the reaction was stirred 30 minutes at −78° C. warmed to room temperature for 1 hr The reaction was then quenched with water (40 mL) extracted with ethyl acetate (50 mL) The organic layer was washed with 1N HCl (2×30 mL) and brine (2×30 mL) dried over sodium sulfate filtered concentrated Purification of the residue by flash chromatography on silica gel (0 to 60% ethyl acetate/hexanes)