2-(2-bromo-5-fluorophenyl)acetaldehyde

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

Procedure: To a solution of 21a (3.60 g, 16.6 mmol) in methanol (40 mL) was added sodium borohydride (640 mg, 16.6 mmol) at 0° C., and the mixture was stirred at room temperature for 1 h. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added dichloromethane (50 mL), diisopropylethylamine (3.5 mL, 20 mmol) and chloromethyl methyl ether (1.5 mL, 20 mmol) at 0° C., and the reaction mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate) to give 22a (2.99 g, 2 steps 68%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ (ppm) 3.04 (t, J=6.7 Hz, 2H), 3.31 (s, 3H), 3.77 (t, J=6.7 Hz, 2H), 4.62 (s, 2H), 6.82 (td, J=8.2, 3.2 Hz, 1H), 7.04 (dd, J=9.4, 2.9 Hz, 1H), 7.48 (dd, J=8.8, 5.3 Hz, 1H). the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the reaction mixture was stirred at room temperature overnight the mixture was extracted with chloroform The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate)

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

Procedure: To a solution of 21a (3.60 g, 16.6 mmol) in methanol (40 mL) was added sodium borohydride (640 mg, 16.6 mmol) at 0° C., and the mixture was stirred at room temperature for 1 h. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added dichloromethane (50 mL), diisopropylethylamine (3.5 mL, 20 mmol) and chloromethyl methyl ether (1.5 mL, 20 mmol) at 0° C., and the reaction mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate) to give 22a (2.99 g, 2 steps 68%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ (ppm) 3.04 (t, J=6.7 Hz, 2H), 3.31 (s, 3H), 3.77 (t, J=6.7 Hz, 2H), 4.62 (s, 2H), 6.82 (td, J=8.2, 3.2 Hz, 1H), 7.04 (dd, J=9.4, 2.9 Hz, 1H), 7.48 (dd, J=8.8, 5.3 Hz, 1H). the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the reaction mixture was stirred at room temperature overnight the mixture was extracted with chloroform The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate)

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

Procedure: To a solution of 21a (3.60 g, 16.6 mmol) in methanol (40 mL) was added sodium borohydride (640 mg, 16.6 mmol) at 0° C., and the mixture was stirred at room temperature for 1 h. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added dichloromethane (50 mL), diisopropylethylamine (3.5 mL, 20 mmol) and chloromethyl methyl ether (1.5 mL, 20 mmol) at 0° C., and the reaction mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate) to give 22a (2.99 g, 2 steps 68%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ (ppm) 3.04 (t, J=6.7 Hz, 2H), 3.31 (s, 3H), 3.77 (t, J=6.7 Hz, 2H), 4.62 (s, 2H), 6.82 (td, J=8.2, 3.2 Hz, 1H), 7.04 (dd, J=9.4, 2.9 Hz, 1H), 7.48 (dd, J=8.8, 5.3 Hz, 1H). the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the reaction mixture was stirred at room temperature overnight the mixture was extracted with chloroform The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate)

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

Procedure: To a solution of 21a (3.60 g, 16.6 mmol) in methanol (40 mL) was added sodium borohydride (640 mg, 16.6 mmol) at 0° C., and the mixture was stirred at room temperature for 1 h. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added dichloromethane (50 mL), diisopropylethylamine (3.5 mL, 20 mmol) and chloromethyl methyl ether (1.5 mL, 20 mmol) at 0° C., and the reaction mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate) to give 22a (2.99 g, 2 steps 68%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ (ppm) 3.04 (t, J=6.7 Hz, 2H), 3.31 (s, 3H), 3.77 (t, J=6.7 Hz, 2H), 4.62 (s, 2H), 6.82 (td, J=8.2, 3.2 Hz, 1H), 7.04 (dd, J=9.4, 2.9 Hz, 1H), 7.48 (dd, J=8.8, 5.3 Hz, 1H). the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the reaction mixture was stirred at room temperature overnight the mixture was extracted with chloroform The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (15:1 hexane/ethyl acetate)