Sodium Hydroxide → 2-(4-Fluoro-2-methylphenoxy)-2-methylpropanoic acid

A solution of 4-fluoro-2-methylphenol (10 g, 79.28 mmol), ethyl 2-bromoisobutyrate (23.2 mL, 158.6 mmol), potassium carbonate (21.9 g, 158.6 mmol), and DMSO (80 mL) was stirred at room temperature for 72 hours. Water and ethyl acetate were added and the layers were separated. The aqueous phase was extracted with ethyl acetate (3×50 mL) and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to afford ethyl 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoate. To a solution of ethyl 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoate (13.3 g, 55.44 mmol) in tetrahydrofuran (40 mL) and methanol (10 mL) was added NaOH (6.66 g, 166.32 mmol) in water (14 mL) and stirred overnight. The volatiles were removed in vacuo and acidified with concentrated HCl. The milky white solution was extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated in vacuo to give 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoic acid (658) as a yellow solid.

1. customThe volatiles were removed in vacuo
2. extractionThe milky white solution was extracted with ethyl acetate
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo

ORD record

ord-bec430d602284d21b28b8e426173c06f

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299117B2