3-溴-2,6-二氟苯甲醛

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-bromo-2,6-difluorobenzaldehyde (2.00 g, 9.05 mmol), 2-methyl-2-propanethiol (0.917 mL, 8.13 mmol), and potassium carbonate (1.5 g, 11 mmol) in DMF (6 mL) was heated to 50° C. overnight in a sealed tube. The material was extracted with EtOAc, and washed with water (3×). Purification of the organic layer by column chromatography (1 to 2% EtOAc:hexanes) afforded 1.2 g (51%) of the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 1.34 (s, 9 H), 7.07-7.16 (m, 1 H), 7.91 (dd, J=9.0, 5.2 Hz, 1H), 10.56-10.63 (m, 1 H). The material was extracted with EtOAc washed with water (3×) Purification of the organic layer by column chromatography (1 to 2% EtOAc:hexanes)

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-bromo-2,6-difluorobenzaldehyde (2.00 g, 9.05 mmol), 2-methyl-2-propanethiol (0.917 mL, 8.13 mmol), and potassium carbonate (1.5 g, 11 mmol) in DMF (6 mL) was heated to 50° C. overnight in a sealed tube. The material was extracted with EtOAc, and washed with water (3×). Purification of the organic layer by column chromatography (1 to 2% EtOAc:hexanes) afforded 1.2 g (51%) of the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 1.34 (s, 9 H), 7.07-7.16 (m, 1 H), 7.91 (dd, J=9.0, 5.2 Hz, 1H), 10.56-10.63 (m, 1 H). The material was extracted with EtOAc washed with water (3×) Purification of the organic layer by column chromatography (1 to 2% EtOAc:hexanes)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-bromo-2,6-difluorobenzaldehyde (2.00 g, 9.05 mmol), 2-methyl-2-propanethiol (0.917 mL, 8.13 mmol), and potassium carbonate (1.5 g, 11 mmol) in DMF (6 mL) was heated to 50° C. overnight in a sealed tube. The material was extracted with EtOAc, and washed with water (3×). Purification of the organic layer by column chromatography (1 to 2% EtOAc:hexanes) afforded 1.2 g (51%) of the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 1.34 (s, 9 H), 7.07-7.16 (m, 1 H), 7.91 (dd, J=9.0, 5.2 Hz, 1H), 10.56-10.63 (m, 1 H). The material was extracted with EtOAc washed with water (3×) Purification of the organic layer by column chromatography (1 to 2% EtOAc:hexanes)

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 13 (150 mg, 0.607 mmol) in toluene 15 mL was added 3-bromo-2, 6-difluorobenzaldehyde 40 (81.4 mg, 0.607 mmol) and subsequently PTSA (230.9 mg, 1.214 mmol) was added, and stirred at 120° C. for 6 h. The reaction mass was diluted with ethyl acetate and washed with water (3×25 mL). The organic layer was dried over sodium sulphate and concentrated to get the crude compound 41. The crude 41 was purified through flash chromatography by using 100-200 mesh silica gel. The compound (E)-2-(3-bromo-2,6-difluorobenzylidene)-6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one 41 was eluted at 32% ethyl acetate in hexane to afford yellow coloured solid. was added washed with water (3×25 mL) The organic layer was dried over sodium sulphate concentrated

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 13 (150 mg, 0.607 mmol) in toluene 15 mL was added 3-bromo-2, 6-difluorobenzaldehyde 40 (81.4 mg, 0.607 mmol) and subsequently PTSA (230.9 mg, 1.214 mmol) was added, and stirred at 120° C. for 6 h. The reaction mass was diluted with ethyl acetate and washed with water (3×25 mL). The organic layer was dried over sodium sulphate and concentrated to get the crude compound 41. The crude 41 was purified through flash chromatography by using 100-200 mesh silica gel. The compound (E)-2-(3-bromo-2,6-difluorobenzylidene)-6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one 41 was eluted at 32% ethyl acetate in hexane to afford yellow coloured solid. was added washed with water (3×25 mL) The organic layer was dried over sodium sulphate concentrated

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 13 (150 mg, 0.607 mmol) in toluene 15 mL was added 3-bromo-2,6-difluorobenzaldehyde 40 (81.4 mg, 0.607 mmol) and subsequently PTSA (230.9 mg, 1.214 mmol) was added, and stirred at 120° C. for 6 h. The reaction mass was diluted with ethyl acetate and washed with water (3×25 mL). The organic layer was dried over sodium sulphate and concentrated to get the crude compound 41. The crude 41 was purified through flash chromatography by using 100-200 mesh silica gel. The compound (E)-2-(3-bromo-2,6-difluorobenzylidene)-6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one 41 was eluted at 32% ethyl acetate in hexane to afford yellow coloured solid. was added washed with water (3×25 mL) The organic layer was dried over sodium sulphate concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 20 g of 3-bromo-2,6-difluorobenzaldehyde are dissolved in 450 ml of methanol and cooled in an ice bath; 3.42 g of sodium borohydride are then added thereto, portionwise. The mixture is stirred at ambient temperature for 1 hour and the solvent is then evaporated off under reduced pressure. The residue is taken up between water and dichloromethane. The organic phase is separated, dried and concentrated under reduced pressure. The residue is crystallized from n-pentane. 14.6 g of compound are obtained. cooled in an ice bath the solvent is then evaporated off under reduced pressure The organic phase is separated dried concentrated under reduced pressure The residue is crystallized from n-pentane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 20 g of 3-bromo-2,6-difluorobenzaldehyde are dissolved in 450 ml of methanol and cooled in an ice bath; 3.42 g of sodium borohydride are then added thereto, portionwise. The mixture is stirred at ambient temperature for 1 hour and the solvent is then evaporated off under reduced pressure. The residue is taken up between water and dichloromethane, and the organic phase organic is separated, dried, and concentrated under reduced pressure. The residue is crystallized from n-pentane. 14.6 g of compound, used as it is in the subsequent stage, are obtained. cooled in an ice bath the solvent is then evaporated off under reduced pressure the organic phase organic is separated dried concentrated under reduced pressure The residue is crystallized from n-pentane are obtained

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 20 g of 3-bromo-2,6-difluorobenzaldehyde are dissolved in 450 ml of methanol and cooled in an ice bath; 3.42 g of sodium borohydride are then added portionwise thereto. The mixture is stirred at ambient temperature for 1 hour and then the solvent is evaporated under reduced pressure. The residue is taken up between water and dichloromethane and the organic phase is separated, dried and concentrated under reduced pressure. The residue is crystallised from n-pentane. 14.6 g of compound are obtained. cooled in an ice bath the solvent is evaporated under reduced pressure the organic phase is separated dried concentrated under reduced pressure The residue is crystallised from n-pentane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-bromo-2,6-difluorobenzaldehyde (5 g) in tetrahydrofuran (50 ml) was added dropwise methylmagnesium bromide (1 M tetrahydrofuran solution, 24.9 ml) at 0° C., and the mixture was stirred for 30 min. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (4.91 g). the mixture was extracted with ethyl acetate The organic layer was washed with saturated aqueous ammonium chloride solution and saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)