3-Fluoro-4-(methylthio)benzaldehyde synthesis

Yield:-

Reaction Conditions:

in acetonitrile; for 19 h;

Steps:

Preparation 49: 3-Fluoro-4-methanesulfinylbenzoic acid and 3-fluoro-4-methylsulfonylbenzoic acid : A stirred solution of 3,4-difluorobenzaldehyde (5.0 g, 35.2 mmol) in dry acetonitrile (50 mL) under argon was treated portionwise with with sodium thiomethoxide (2.47 g, 35.2 mmol) over approximately 1 h. After 18 h the reaction mixture was diluted with EtOAc (50 mL) and washed with saturated aqueous NaHCO₃ (2 x 10 mL) and saturated aqueous NH₄Cl (20 mL). The organic phase was dried (MgSO₄), evaporated and the residue purified by column chromatography (IH-EtOAc 9:1 then 7:3) to give 3-fluoro-4-methylsulfanylbenzaldehyde: δ_H (CDCl₃) 2.54 (3H, s), 7.32 (IH, t), 7.51 (IH, dd), 7.63 (IH, dd), 9.92 (IH, d). A sample of this thioether (1.0 g, 5.38 mmol) was suspended in water and NaH₂PO₄ (705 mg, 5.88 mmol), tert- butanol (44 mL) and sodium chlorite (1.59 g, 63 mmol) were then added. After stirring vigorously for 1.5 h, the tert-butanol was removed under reduced pressure and EtOAc (50 mL) added. The mixture was extracted with 1 M aqueous NaOH (3 x 20 mL) and the combined extracts acidified to pH 2 using dilute HCl. The precipitate was extracted into EtOAc which was dried (MgSO₄) and evaporated to afford an inseparable mixture of the the title sulfoxide: RT = 2.22 min (method 2); m/z (ES⁺) = 203.0 [M+H]⁺ and the sulfone 2.22 min (method 2); m/z (ES⁺) = 219.0 [M+H]⁺.

References:

WO2007/3960,2007,A1 Location in patent:Page/Page column 33-34