(5,6-difluoro-2,2-dimethyl-3H-1-benzofuran-7-yl)methanol

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

Procedure: To a solution of (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.18 g, 0.84 mmol) in anhydrous dichloromethane (5 mL) was added SOCl2 dropwise at 0° C. The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuo, and the residue was dissolved in EtOAc (100 mL). The solution was washed with water (30 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo to give a solid 7-(chloromethyl)-5,6-difluoro-2,2-dimethyl-2,3-dihydrobenzofuran (737) (0.194 g, 99%). The solvent was removed in vacuo the residue was dissolved in EtOAc (100 mL) The solution was washed with water (30 mL) dried over anhydrous sodium sulfate evaporated in vacuo

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

Procedure: To 5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-carboxylic acid (735) (0.75 g, 3.29 mmol) was added 1.0 M of borane tetrahydrofuran complex solution (12 mL), and the mixture was stirred at room temperature overnight. The reaction was cooled to 0° C., acidified with 5 N HCl to pH 1, and then neutralized to pH 8 with 5 N NaOH. The mixture was extracted with EtOAc (80 mL×3) and the combined organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The product was purified by prep HPLC to yield (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.4 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ 7.18 (t, J=9.0 Hz, 1H), 4.38 (s, 2H), 2.97 (s, 2H), 1.40 (s, 6H). The reaction was cooled to 0° C. The mixture was extracted with EtOAc (80 mL×3) the combined organic phase was washed with water (50 mL) dried over anhydrous sodium sulfate the solvent removed in vacuo The product was purified by prep HPLC

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

Procedure: To a solution of (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.18 g, 0.84 mmol) in anhydrous dichloromethane (5 mL) was added SOCl2 dropwise at 0° C. The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuo, and the residue was dissolved in EtOAc (100 mL). The solution was washed with water (30 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo to give a solid 7-(chloromethyl)-5,6-difluoro-2,2-dimethyl-2,3-dihydrobenzofuran (737) (0.194 g, 99%). The solvent was removed in vacuo the residue was dissolved in EtOAc (100 mL) The solution was washed with water (30 mL) dried over anhydrous sodium sulfate evaporated in vacuo

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

Procedure: To 5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-carboxylic acid (735) (0.75 g, 3.29 mmol) was added 1.0 M of borane tetrahydrofuran complex solution (12 mL), and the mixture was stirred at room temperature overnight. The reaction was cooled to 0° C., acidified with 5 N HCl to pH 1, and then neutralized to pH 8 with 5 N NaOH. The mixture was extracted with EtOAc (80 mL×3) and the combined organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The product was purified by prep HPLC to yield (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.4 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ 7.18 (t, J=9.0 Hz, 1H), 4.38 (s, 2H), 2.97 (s, 2H), 1.40 (s, 6H). The reaction was cooled to 0° C. The mixture was extracted with EtOAc (80 mL×3) the combined organic phase was washed with water (50 mL) dried over anhydrous sodium sulfate the solvent removed in vacuo The product was purified by prep HPLC

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

Procedure: To a solution of (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.18 g, 0.84 mmol) in anhydrous dichloromethane (5 mL) was added SOCl2 dropwise at 0° C. The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuo, and the residue was dissolved in EtOAc (100 mL). The solution was washed with water (30 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo to give a solid 7-(chloromethyl)-5,6-difluoro-2,2-dimethyl-2,3-dihydrobenzofuran (737) (0.194 g, 99%). The solvent was removed in vacuo the residue was dissolved in EtOAc (100 mL) The solution was washed with water (30 mL) dried over anhydrous sodium sulfate evaporated in vacuo

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

Procedure: To 5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-carboxylic acid (735) (0.75 g, 3.29 mmol) was added 1.0 M of borane tetrahydrofuran complex solution (12 mL), and the mixture was stirred at room temperature overnight. The reaction was cooled to 0° C., acidified with 5 N HCl to pH 1, and then neutralized to pH 8 with 5 N NaOH. The mixture was extracted with EtOAc (80 mL×3) and the combined organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The product was purified by prep HPLC to yield (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.4 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ 7.18 (t, J=9.0 Hz, 1H), 4.38 (s, 2H), 2.97 (s, 2H), 1.40 (s, 6H). The reaction was cooled to 0° C. The mixture was extracted with EtOAc (80 mL×3) the combined organic phase was washed with water (50 mL) dried over anhydrous sodium sulfate the solvent removed in vacuo The product was purified by prep HPLC

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

Procedure: To a solution of (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.18 g, 0.84 mmol) in anhydrous dichloromethane (5 mL) was added SOCl2 dropwise at 0° C. The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuo, and the residue was dissolved in EtOAc (100 mL). The solution was washed with water (30 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo to give a solid 7-(chloromethyl)-5,6-difluoro-2,2-dimethyl-2,3-dihydrobenzofuran (737) (0.194 g, 99%). The solvent was removed in vacuo the residue was dissolved in EtOAc (100 mL) The solution was washed with water (30 mL) dried over anhydrous sodium sulfate evaporated in vacuo

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

Procedure: To 5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-carboxylic acid (735) (0.75 g, 3.29 mmol) was added 1.0 M of borane tetrahydrofuran complex solution (12 mL), and the mixture was stirred at room temperature overnight. The reaction was cooled to 0° C., acidified with 5 N HCl to pH 1, and then neutralized to pH 8 with 5 N NaOH. The mixture was extracted with EtOAc (80 mL×3) and the combined organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The product was purified by prep HPLC to yield (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.4 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ 7.18 (t, J=9.0 Hz, 1H), 4.38 (s, 2H), 2.97 (s, 2H), 1.40 (s, 6H). The reaction was cooled to 0° C. The mixture was extracted with EtOAc (80 mL×3) the combined organic phase was washed with water (50 mL) dried over anhydrous sodium sulfate the solvent removed in vacuo The product was purified by prep HPLC

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

Procedure: To a solution of (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.18 g, 0.84 mmol) in anhydrous dichloromethane (5 mL) was added SOCl2 dropwise at 0° C. The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuo, and the residue was dissolved in EtOAc (100 mL). The solution was washed with water (30 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo to give a solid 7-(chloromethyl)-5,6-difluoro-2,2-dimethyl-2,3-dihydrobenzofuran (737) (0.194 g, 99%). The solvent was removed in vacuo the residue was dissolved in EtOAc (100 mL) The solution was washed with water (30 mL) dried over anhydrous sodium sulfate evaporated in vacuo

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

Procedure: To 5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-carboxylic acid (735) (0.75 g, 3.29 mmol) was added 1.0 M of borane tetrahydrofuran complex solution (12 mL), and the mixture was stirred at room temperature overnight. The reaction was cooled to 0° C., acidified with 5 N HCl to pH 1, and then neutralized to pH 8 with 5 N NaOH. The mixture was extracted with EtOAc (80 mL×3) and the combined organic phase was washed with water (50 mL), dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The product was purified by prep HPLC to yield (5,6-difluoro-2,2-dimethyl-3H-benzofuran-7-yl)methanol (736) (0.4 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ 7.18 (t, J=9.0 Hz, 1H), 4.38 (s, 2H), 2.97 (s, 2H), 1.40 (s, 6H). The reaction was cooled to 0° C. The mixture was extracted with EtOAc (80 mL×3) the combined organic phase was washed with water (50 mL) dried over anhydrous sodium sulfate the solvent removed in vacuo The product was purified by prep HPLC