3-bromo-2,5-difluorobenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 4-amino-3-bromo-2,5-difluorobenzaldehyde (3.4 g, 14.3 mmol) was dissolved in acetic acid (18 mL) before addition of hypophosphoric acid (50% in water, 39 mL). A solution of sodium nitrite (1.4 eq, 1.4 g) in water (8 mL) was then added dropwise under ice-cooling. After stirring at rt for 2 h, the reaction mixture was poured onto a mixture ice/water and the aqueous phase extracted with DCM. The combined organic phases were dried over sodium sulfate and evaporated. A column chromatography (0 to 10% ethyl acetate in petroleum ether) afforded 3-bromo-2,5-difluorobenzaldehyde (1.3 g, 6.3 mmol, 44%). 1H NMR (d6-DMSO) δ 10.15-10.12 (m, 1H), 8.13 (ddd, J=8.0, 5.0, 3.0 Hz, 1H), 7.66 (ddd, J=8.0, 5.0, 3.0 Hz, 1H). cooling the aqueous phase extracted with DCM The combined organic phases were dried over sodium sulfate evaporated

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

実験手順: 4-amino-3-bromo-2,5-difluorobenzaldehyde (3.4 g, 14.3 mmol) was dissolved in acetic acid (18 mL) before addition of hypophosphoric acid (50% in water, 39 mL). A solution of sodium nitrite (1.4 eq, 1.4 g) in water (8 mL) was then added dropwise under ice-cooling. After stirring at rt for 2 h, the reaction mixture was poured onto a mixture ice/water and the aqueous phase extracted with DCM. The combined organic phases were dried over sodium sulfate and evaporated. A column chromatography (0 to 10% ethyl acetate in petroleum ether) afforded 3-bromo-2,5-difluorobenzaldehyde (1.3 g, 6.3 mmol, 44%). 1H NMR (d6-DMSO) δ 10.15-10.12 (m, 1H), 8.13 (ddd, J=8.0, 5.0, 3.0 Hz, 1H), 7.66 (ddd, J=8.0, 5.0, 3.0 Hz, 1H). cooling the aqueous phase extracted with DCM The combined organic phases were dried over sodium sulfate evaporated

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

実験手順: 4-amino-3-bromo-2,5-difluorobenzaldehyde (3.4 g, 14.3 mmol) was dissolved in acetic acid (18 mL) before addition of hypophosphoric acid (50% in water, 39 mL). A solution of sodium nitrite (1.4 eq, 1.4 g) in water (8 mL) was then added dropwise under ice-cooling. After stirring at rt for 2 h, the reaction mixture was poured onto a mixture ice/water and the aqueous phase extracted with DCM. The combined organic phases were dried over sodium sulfate and evaporated. A column chromatography (0 to 10% ethyl acetate in petroleum ether) afforded 3-bromo-2,5-difluorobenzaldehyde (1.3 g, 6.3 mmol, 44%). 1H NMR (d6-DMSO) δ 10.15-10.12 (m, 1H), 8.13 (ddd, J=8.0, 5.0, 3.0 Hz, 1H), 7.66 (ddd, J=8.0, 5.0, 3.0 Hz, 1H). cooling the aqueous phase extracted with DCM The combined organic phases were dried over sodium sulfate evaporated

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

実験手順: 4-amino-3-bromo-2,5-difluorobenzaldehyde (3.4 g, 14.3 mmol) was dissolved in acetic acid (18 mL) before addition of hypophosphoric acid (50% in water, 39 mL). A solution of sodium nitrite (1.4 eq, 1.4 g) in water (8 mL) was then added dropwise under ice-cooling. After stirring at rt for 2 h, the reaction mixture was poured onto a mixture ice/water and the aqueous phase extracted with DCM. The combined organic phases were dried over sodium sulfate and evaporated. A column chromatography (0 to 10% ethyl acetate in petroleum ether) afforded 3-bromo-2,5-difluorobenzaldehyde (1.3 g, 6.3 mmol, 44%). 1H NMR (d6-DMSO) δ 10.15-10.12 (m, 1H), 8.13 (ddd, J=8.0, 5.0, 3.0 Hz, 1H), 7.66 (ddd, J=8.0, 5.0, 3.0 Hz, 1H). cooling the aqueous phase extracted with DCM The combined organic phases were dried over sodium sulfate evaporated

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a stirred mixture of 13.3 g of 3-bromo-2,5-difluorobenzaldehyde and 300 mL of THF cooled to -35°/-20° under an N2 atmosphere is added 30 mL of 2.85M of MeMgBr in Et2O over 10 minutes. The cooling bath is removed and the mixture stirred 1 hour and finally poured into 1 L of ice/H2O. 10% HCl is added to bring the pH to ~2 and the mixture extracted with 3×200 ml of CH2Cl2. The CH2Cl2 extracts are washed with H2O, saturated NaHCO3, H2O (250 mL each) and stripped to furnish 14.5 g of crude 3-bromo-2,5-difluoro-α-methylbenzyl alcohol. M+1 ions are observed at 236 and 238 in the mass spectrum. The crude material is used directly in the next step. cooled to -35°/-20° under an N2 atmosphere The cooling bath is removed finally poured into 1 L of ice/H2O 10% HCl is added the mixture extracted with 3×200 ml of CH2Cl2 The CH2Cl2 extracts are washed with H2O, saturated NaHCO3, H2O (250 mL each)

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

実験手順: A mixture of 16 g of 4-amino-3-bromo-2,5-difluorobenzaldehyde and 375 mL of AcOH is stirred until homogenous and 188 mL of 50-52% aqueous hypophosphorous acid is added. Next a solution of 6.8 g of NaNO2 in 38 mL of H2O is added dropwise over 15 minutes with ice cooling to maintain a temperature of 15°-20° C. The ice bath is removed and stirring continued for 1 hour. the reaction mixture is poured into 1 L of ice/H2O and extracted with 3×300 mL of CH2Cl2. The CH2Cl2 extracts are washed with H2O, 2×10% NaOH, and 2×H2O (250 mL each), dried with Na2SO4 and concentrated in vacuo to give 13.32 g (80% yield) of 3-bromo-2,5-difluorobenzaldehyde, m.p. 36°-38° C. Recrystallization from Et2O/hexane furnishes the title compound melting at 37°-40° C. with M+1 ions at 221 and 223 in the mass spectrum. is added to maintain a temperature of 15°-20° C The ice bath is removed the reaction mixture is poured into 1 L of ice/H2O extracted with 3×300 mL of CH2Cl2 The CH2Cl2 extracts are washed with H2O, 2×10% NaOH, and 2×H2O (250 mL each) dried with Na2SO4 concentrated in vacuo

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

実験手順: 4-amino-3-bromo-2,5-difluorobenzaldehyde (3.4 g, 14.3 mmol) was dissolved in acetic acid (18 mL) before addition of hypophosphoric acid (50% in water, 39 mL). A solution of sodium nitrite (1.4 eq, 1.4 g) in water (8 mL) was then added dropwise under ice-cooling. After stirring at rt for 2 h, the reaction mixture was poured onto a mixture ice/water and the aqueous phase extracted with DCM. The combined organic phases were dried over sodium sulfate and evaporated. A column chromatography (0 to 10% ethyl acetate in petroleum ether) afforded 3-bromo-2,5-difluorobenzaldehyde (1.3 g, 6.3 mmol, 44%). 1H NMR (d6-DMSO) δ 10.15-10.12 (m, 1H), 8.13 (ddd, J=8.0, 5.0, 3.0 Hz, 1H), 7.66 (ddd, J=8.0, 5.0, 3.0 Hz, 1H). cooling the aqueous phase extracted with DCM The combined organic phases were dried over sodium sulfate evaporated