bromo(fluoro)methane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.5 g of 80% strength sodium hydride in mineral oil are added in portions at 20° C. with stirring to a solution of 12.5 g (60 mmol) of methyl 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-acrylate and 30 g of methyl formate in 150 ml of dry dimethylformamide in a three-necked flask having an attached condenser. After approximately one hour, the exothermic reaction commences with foaming. The temperature is kept at 40° C. for 3 hours. The mixture is cooled to 0-5° C. and treated successively with 4.8 g (0.05 mol) of methanesulphonic acid and in portions with 13.8 g (0.1 mol) of potassium carbonate. The temperature of the cooling fluid in the condenser, as well as the temperature of the reaction mixture, is then adjusted to 0° C. Using a syringe, 6.8 g (0.06 mol) of bromofluoromethane are added and the mixture is stirred overnight at 0-5° C. The reaction mixture is stirred for a further 24 hours without cooling. The temperature of the cooling fluid is kept at approximately 0° C. The mixture is concentrated, the residue is taken up using ethyl acetate, the solution is washed with water, and the organic phase is dried over sodium sulphate and concentrated again. The residue is chromatographed on silica gel using hexane/acetone (7:3). 11.6 g (75% of theory) of methyl 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-3-fluoromethoxy-acrylate are obtained. the exothermic reaction commences with foaming The temperature is kept at 40° C. for 3 hours is then adjusted to 0° C The reaction mixture is stirred for a further 24 hours without cooling is kept at approximately 0° C The mixture is concentrated the solution is washed with water the organic phase is dried over sodium sulphate concentrated again The residue is chromatographed on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14.2 g of potassium carbonate was added to a solution of 14.5 g of methyl 2-hydroxyimino-acetoacetate in 50 ml of dimethylsulfoxide, and then 11.6 g of fluoro-bromomethane in 9 ml of N,N-dimethylformamide was added dropwise thereto. The mixture was stirred for 1 hour 30 minutes at room temperature, then poured into ice-water, and the resultant mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated saline, dried over Na2SO4 and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (120 g) with a mixture solvent of ethyl acetate and toluene (1/4 volume) as a eluent to give 4.7 g (27% yield) of methyl 2-fluoromethoxyiminoaceto-acetate (syn isomer). the resultant mixture was extracted twice with ethyl acetate The organic layer was washed with saturated saline dried over Na2SO4 concentrated under reduced pressure to remove the solvent The residue was purified by silica gel column chromatography (120 g) with a mixture solvent of ethyl acetate and toluene (1/4 volume) as a eluent

Conditions: temp:0.00; pressure:0.00; stir: