O-Cresol → Ethyl 2-(2-methylphenoxy)acetate

Temperature

0 °C

An oven-dried 300 mL round-bottomed flask was charged with 2-methylphenol (15.0 g, 139 mmol), finely powdered K2CO3 (38.3 g, 277 mmol), and anhydrous DMF (60 mL) and the resulting solution was cooled to 0° C. Next, ethyl bromoacetate (18.5 mL, 167 mmol) was added dropwise at 0° C., and the reaction was stirred vigorously at room temperature for 1 h. The reaction mixture was cooled using an ice-water bath, water (180 mL) was added and the product was extracted twice with AcOEt (200 mL and 100 mL). The combined organics were sequentially washed with 2×100 mL of water and 100 mL of brine, dried over Na2SO4, and concentrated to a slightly yellow oil which was then purified by flash chromatography (SiO2 gel 60 N, eluted with 5% AcOEt/hexane-10% AcOEt/hexane). The fractions containing only desired product were combined and concentrated to provide compound 10.1 as a colorless oil (29.3 g). 1H NMR (300 MHz) (CDCl3) δ 7.26-7.13 (2H, m); 6.90 (1H, t, J=7.3 Hz); 6.71 (1H, d, J=8.0 Hz); 4.63 (2H, s); 4.27 (2H, q, J=6.9 Hz); 2.30 (3H, s); 1.30 (3H, t, J=6.9 Hz).

1. temperatureThe reaction mixture was cooled
2. extractionthe product was extracted twice with AcOEt (200 mL and 100 mL)
3. washThe combined organics were sequentially washed with 2×100 mL of water and 100 mL of brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated to a slightly yellow oil which
6. customwas then purified by flash chromatography (SiO2 gel 60 N, eluted with 5% AcOEt/hexane-10% AcOEt/hexane)
7. additionThe fractions containing only desired product
8. concentrationconcentrated

ORD record

ord-fc1cb66b1362496989b7f2e6aa1fa644

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07645779B2