Water → Acetic acid, 5-methoxy-m-tolyl-

A solution of 1-bromomethyl-3-methoxy-5-methyl-benzene (1.66 g, 7.7 mmol) and sodium cyanide (1.89 g, 38.5 mmol) in ethanol (15 mL) and water (5 mL) was warmed to 60° C. for 2 hrs. The reaction mixture was cooled, concentrated in vacuo, diluted with water (100 mL), and extracted with methylene chloride (3×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 1.16 g of a light yellow oil. The crude 1-cyanomethyl-3-methoxy-5-methyl-benzene (1.16 g, 7.1 mmol) and sodium hydroxide (1.44 g, 35.9 mmol) in ethanol (20 mL) and water (10 mL) was refluxed overnight. The reaction mixture was cooled, concentrated in vacuo, diluted with water, and extracted with methylene chloride (3×10 mL). The aqueous layer was acidified to pH 2 with 6N hydrochloric acid and extracted with methylene chloride (3×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 0.86 g (62% for 2 steps) of (3-methoxy-5-methyl-phenyl)-acetic acid as an off white solid. This material was used without further purification: 1H NMR (300 MHz) compatible.

1. temperatureThe reaction mixture was cooled
2. concentrationconcentrated in vacuo
3. additiondiluted with water
4. extractionextracted with methylene chloride (3×10 mL)
5. extractionextracted with methylene chloride (3×20 mL)
6. dry with materialThe combined organic layers were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-f2f99fe4585548a08fcfe640e99a4521

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067529B2