tert-butyl 3-(4-methoxyphenyl)propanoate

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)

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

Procedure: To a fast stirring suspension of anhydrous magnesium sulfate (4.81 g, 40.0 mmol) in dichloromethane (40 ml) was added sulfuric acid (0.55 ml, 10.32 mmol). The reaction was vigorously stirred for 15 minutes at room temperature and then 3-(4-methoxyphenyl)propionic acid (1.8 g, 9.99 mmol) and tert-butanol (4.78 ml, 50.0 mmol) were added. The reaction was sealed and stirred at room temperature overnight. The reaction was quenched with 75 mL of saturated sodium bicarbonate solution and washed with water (2×50 mL) and brine (1×50 mL). The organic layer was dried over sodium sulfate, filtered, concentrated, and purified by flash chromatography on silica gel (0 to 80% ethyl acetate/hexanes) to afford tert-butyl 3-(4-methoxyphenyl)propanoate. 1H NMR (CDCl3, 500 MHz) δ 7.11 (d, J=8.7 Hz, 2H), 6.82 (d, J=8.7 Hz, 2H), 3.78 (s, 3H), 2.85 (t, J=7.7 Hz, 2H), 2.50 (t, J=7.7 Hz, 2H), 1.42 (s, 9H). The reaction was vigorously stirred for 15 minutes at room temperature The reaction was sealed stirred at room temperature overnight The reaction was quenched with 75 mL of saturated sodium bicarbonate solution washed with water (2×50 mL) and brine (1×50 mL) The organic layer was dried over sodium sulfate filtered concentrated purified by flash chromatography on silica gel (0 to 80% ethyl acetate/hexanes)