Methyl iodide → 1-tert-butyl-3-methoxybenzene

To a solution of 3-tert-butylphenol (5.0 g; 33.28 mmol) in N,N-dimethylformamide (166 mL) at room temperature under nitrogen was added sodium hydride (2.0 g; 49.92 mmol). The reaction mixture was stirred at room temperature for 10 minutes and then iodomethane (6.2 mL; 99.84 mmol) was added. After stirring at room temperature overnight, the reaction mixture was quenched with water and aqueous hydrochloric acid (2N) and extracted with ethyl acetate. The combined organic phases were successively washed with water and aqueous saturated sodium chloride, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the resulting crude residue was purified by automated silica gel column chromatography (Biotage®) eluting with ethyl acetate/hexanes (0 to 40% v/v over 400 mL gradient elution) to yield the title product as a clear oil (6.19 g).

1. stirringAfter stirring at room temperature overnight
2. customthe reaction mixture was quenched with water and aqueous hydrochloric acid (2N)
3. extractionextracted with ethyl acetate
4. washThe combined organic phases were successively washed with water and aqueous saturated sodium chloride
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe resulting crude residue was purified by automated silica gel column chromatography (Biotage®)
9. washeluting with ethyl acetate/hexanes (0 to 40% v/v over 400 mL gradient elution)

ORD record

ord-f836bcf7d034451993820f468b25ab4d

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08178699B2