4-BROMO-3-HYDROXYMETHYL-BENZONITRILE

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

Procedure: To a solution of 2-bromo-5-cyanobenzyl alcohol (4.59 g, 21.7 mmol) in dichloromethane (80 mL) were added diisopropylethylamine (5.6 mL, 32 mmol) and chloromethyl methyl ether (2.3 mL, 30 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 (6:1 hexane/ethyl acetate) to give 18f (4.08 g, 71%): 1H NMR (300 MHz, CDCl3) δ (ppm) 3.43 (s, 3H), 4.65 (s, 2H), 4.80 (s, 2H), 7.43 (dd, J=8.2, 4.1 Hz, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.82 (d, J=4.1 Hz, 1H). 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 (6:1 hexane/ethyl acetate)

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

Procedure: To a solution of 2-bromo-5-cyanobenzyl alcohol (4.59 g, 21.7 mmol) in dichloromethane (80 mL) were added diisopropylethylamine (5.6 mL, 32 mmol) and chloromethyl methyl ether (2.3 mL, 30 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 (6:1 hexane/ethyl acetate) to give 18f (4.08 g, 71%): 1H NMR (300 MHz, CDCl3) δ (ppm) 3.43 (s, 3H), 4.65 (s, 2H), 4.80 (s, 2H), 7.43 (dd, J=8.2, 4.1 Hz, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.82 (d, J=4.1 Hz, 1H). 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 (6:1 hexane/ethyl acetate)

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

Procedure: To a solution of 2-bromo-5-cyanobenzyl alcohol (4.59 g, 21.7 mmol) in dichloromethane (80 mL) were added diisopropylethylamine (5.6 mL, 32 mmol) and chloromethyl methyl ether (2.3 mL, 30 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 (6:1 hexane/ethyl acetate) to give 18f (4.08 g, 71%): 1H NMR (300 MHz, CDCl3) δ (ppm) 3.43 (s, 3H), 4.65 (s, 2H), 4.80 (s, 2H), 7.43 (dd, J=8.2, 4.1 Hz, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.82 (d, J=4.1 Hz, 1H). 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 (6:1 hexane/ethyl acetate)

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

Procedure: A mixture of 2 (20.0 mmol), (methoxymethyl)triphenylphosphonium chloride (8.49 g, 24.0 mmol), and potassium tert-butoxide (2.83 g, 24.0 mol) in N,N-dimethylformamide (50 mL) was stirred at room temperature for overnight. The reaction was quenched with 6 N HCl, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (×2) and brine, and dried on anhydrous sodium sulfate. The solvent was removed under reduced. To the residue were added tetrahydrofuran (60 mL) and 6 N HCl, and the mixture was heated at reflux for 8 h. Water was added, and the mixture was extracted with ether. The organic layer was washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure to afford 16.6 mmol of 9. The reaction was quenched with 6 N HCl the mixture was extracted with ethyl acetate The organic layer was washed with water (×2) and brine dried on anhydrous sodium sulfate The solvent was removed To the residue were added tetrahydrofuran (60 mL) and 6 N HCl the mixture was heated at reflux for 8 h Water was added the mixture was extracted with ether The organic layer was washed with brine dried on anhydrous sodium sulfate The solvent was removed under reduced pressure

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

Procedure: To a solution of 2-bromo-5-cyanobenzyl alcohol (4.59 g, 21.7 mmol) in dichloromethane (80 mL) were added diisopropylethylamine (5.6 mL, 32 mmol) and chloromethyl methyl ether (2.3 mL, 30 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 (6:1 hexane/ethyl acetate) to give 18f (4.08 g, 71%): 1H NMR (300 MHz, CDCl3) δ (ppm) 3.43 (s, 3H), 4.65 (s, 2H), 4.80 (s, 2H), 7.43 (dd, J=8.2, 4.1 Hz, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.82 (d, J=4.1 Hz, 1H). 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 (6:1 hexane/ethyl acetate)