2-(5-fluoro-2-methoxyphenyl)acetaldehyde

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-butenylmagnesium bromide (0.5 M in THF, 9 mL, 4.5 mmol) at 0° C. was added a solution of 5-fluoro-2-methoxyphenylacetaldehyde (635 mg, 3.8 mmol) in THF (10 mL) dropwise for 15 min. Then the reaction mixture was poured in to a solution of saturated ammonium chloride (40 mL) in a separatory funnel. The organics were extracted with ethyl acetate (3×50 mL) and the combined organic layers were washed with brine (50 mL) and dried over sodium sulfate. The solvent was removed in vacuo and crude product thus obtained was purified by flash column chromatography (12.5% EtOAc in hexane, Rf=0.18) to give the product as an oil (642 mg, 74%). The organics were extracted with ethyl acetate (3×50 mL) the combined organic layers were washed with brine (50 mL) dried over sodium sulfate The solvent was removed in vacuo and crude product thus obtained was purified by flash column chromatography (12.5% EtOAc in hexane, Rf=0.18)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of methoxymethyltriphenylphosphonium chloride (10.0 g, 30.0 mmol) in THF (30 mL) under Ar was added NaH (60% in mineral oil, 1.2 g, 30 mmol) and then heated to reflux for 1 h. The orange colored suspension was cooled to 0° C. and 5-fluoro-2-methoxybenzaldehyde (4.2 g, 26.0 mmol) was added and the mixture was stirred for 12 h at room temperature. The reaction mixture was then poured into a separatory funnel containing ammonium chloride aqueous solution (sat. NH4Cl/H2O, 1:1, v:v, 100 mL). The organic material was extracted with ethyl acetate (3×80 mL) and the combined organic layers were washed with brine (60 mL) and dried over Na2SO4. The solvent was then removed in vacuo and the crude product (2a) obtained was dissolved in acetone (50 mL). H2SO4 (1 M, 1.5 mL) was then added and the mixture obtained was heated to reflux for 6 h while stirring. The reaction was then cooled to room temperature and the solvent was removed in vacuo to obtain the crude product that was then purified by flash column chromatography (Rf=0.15, EtOAc/Hexane, 10:90, v:v) to afford the product (2.63 g, 66%) as an oil: 1H NMR (CDCl3, 500 MHz): δ 9.68 (s, 1 H), 6.97 (dt, J=3.1, 8.7 Hz, 1 H), 6.89 (dd, J=3.1, 8.7 Hz, 1 H), 6.83 (dd, J=4.3, 8.7 Hz, 1 H), 3.80 (s, 3 H), 3.63 (d, J=1.7 Hz, 2 H). heated to reflux for 1 h The reaction mixture was then poured into a separatory funnel The organic material was extracted with ethyl acetate (3×80 mL) the combined organic layers were washed with brine (60 mL) dried over Na2SO4 The solvent was then removed in vacuo the crude product (2a) obtained the mixture obtained was heated to reflux for 6 h while stirring The reaction was then cooled to room temperature the solvent was removed in vacuo to obtain the crude product that was then purified by flash column chromatography (Rf=0.15, EtOAc/Hexane, 10:90, v:v)