Toluene → Methyl 3-difluoromethoxy-thiophene-2-carboxylate

Temperature

90 °C

At room temperature, a mixture of 10 g (0.063 mol) of methyl 3-hydroxy-thiophene-2-carboxylate and 90 ml of toluene is admixed with a solution of 5.1 g (0.127 mol) of sodium hydroxide in 8 ml of water. The reaction mixture is heated with stirring to 90° C., 1.1 g of tetrabutyl-phosphonium bromide are added and 16.4 g (0.189 mol) of chlorodifluoromethane are introduced over a period of 30 minutes. The mixture is then stirred at 90° C. for one hour. The reaction mixture is subsequently cooled to room temperature and admixed with water. The organic phase is separated off, dried over sodium sulphate and then concentrated under reduced pressure at 50° C. The residue that remains is chromatographed over silica gel using cyclohexane:ethyl acetate=3:1 as mobile phase. Concentration of the eluate gives 4.1 g (31.3% of theory) of methyl 3-difluoromethoxy-thiophene-2-carboxylate in the form of an oil.

1. temperatureThe reaction mixture is heated
2. stirringThe mixture is then stirred at 90° C. for one hour
3. temperatureThe reaction mixture is subsequently cooled to room temperature
4. customThe organic phase is separated off
5. dry with materialdried over sodium sulphate
6. concentrationconcentrated under reduced pressure at 50° C
7. customThe residue that remains is chromatographed over silica gel

ORD record

ord-232a9a77598b4a1d970274b92001e3c5

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06319940B1