Dimethyl Sulfate → N-(4-methoxy-2,3,6-trimethylphenyl)formamide

N-(4-Hydroxy-2,3,6-trimethylphenyl)formamide (30.0 g, 167 mmol) was dissolved into a mixed solvent comprising of a 4 N aqueous solution of potassium hydroxide (100 ml) and methanol (300 ml) and then dimethyl sulfate (42.0 g, 334 mmol) was added into the resulting solution. The mixture was refluxed with heating for 14 hours. The reaction mixture was cooled down and the crystals precipitated were collected by filtration to obtain N-(4-methoxy-2,3,6-trimethylphenyl)formamide as a crude product. To a suspension of this compound in methanol (200 ml) was added concentrated hydrochloric acid (50 ml) and the mixture was refluxed with heating for 3 hours. The reaction mixture was cooled down to room temperature and then neutralized with an 8 N aqueous solution of sodium hydroxide. The product was extracted twice with ethyl acetate. The combined extracts were washed with a 10% aqueous solution of sodium hydrosulfite, dried on magnesium sulfate, and then concentrated under reduced pressure. The residue was crystallized from isopropyl ether to obtain 21.0 g (76% yield) of the title compound. Melting point: 70-72° C.

1. temperatureThe mixture was refluxed
2. temperaturewith heating for 14 hours
3. temperatureThe reaction mixture was cooled down
4. customthe crystals precipitated
5. filtrationwere collected by filtration

ORD record

ord-b9a7c9154cf443ca8b0b6e975051cef4

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06479536B1