6-bromo-1,3-dihydro-2-benzofuran-1-ol

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

Procedure: Step 2) To a solution of compound 145 (2.1 g, 9.77 mmol) in tetrahydrofuran (40.0 mL) was slowly added 4-ethylphenylmagnesium bromide (39 mL, 0.5M solution in THF) at 0° C., and the reaction mixture was stirred for 12 h at room temperature. The resulting mixture was quenched with sat. NH4Cl, diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide (5-bromo-2-(hydroxymethyl)phenyl)(4-ethylphenyl)methanol (146, 1.53 g, 49%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J=2.0 Hz, 1H), 7.42 (dd, J=8.0, 2.0 Hz, 1H), 7.26-7.17 (m, 5H), 5.97 (s, 1H), 4.58 (d, J=12.8 Hz, 1H), 4.43 (d, J=12.4 Hz, 1H), 2.65 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). at 0° C. The resulting mixture was quenched with sat. NH4Cl diluted with EtOAc washed with brine The organic layer was dried over MgSO4 filtered concentrated in vacuo The crude was purified by silica gel column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1) To a solution of 6-bromophthalide (144, 550 mg, 2.58 mmol) in dichloromethane (20.0 mL) was slowly added DIBAL-H (2.7 mL, 1.0M solution in hexane) at −78° C., and the reaction mixture was stirred for 1.5 h at −78° C. The resulting mixture was quenched with sat. Na2SO4 and allowed to warm to room temperature. To the mixture was added anhydrous Na2SO4, and the mixture was stirred for 12 h, then filtered and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide 6-bromo-1,3-dihydroisobenzofuran-1-ol (145, 530 mg, 96%) as yellow oil. at −78° C. The resulting mixture was quenched with sat. Na2SO4 to warm to room temperature To the mixture was added anhydrous Na2SO4 the mixture was stirred for 12 h filtered concentrated in vacuo The crude was purified by silica gel column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1) To a solution of 6-bromophthalide (144, 550 mg, 2.58 mmol) in dichloromethane (20.0 mL) was slowly added DIBAL-H (2.7 mL, 1.0M solution in hexane) at −78° C., and the reaction mixture was stirred for 1.5 h at −78° C. The resulting mixture was quenched with sat. Na2SO4 and allowed to warm to room temperature. To the mixture was added anhydrous Na2SO4, and the mixture was stirred for 12 h, then filtered and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide 6-bromo-1,3-dihydroisobenzofuran-1-ol (145, 530 mg, 96%) as yellow oil. at −78° C. The resulting mixture was quenched with sat. Na2SO4 to warm to room temperature To the mixture was added anhydrous Na2SO4 the mixture was stirred for 12 h filtered concentrated in vacuo The crude was purified by silica gel column chromatography

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

Procedure: Step 2) To a solution of compound 145 (2.1 g, 9.77 mmol) in tetrahydrofuran (40.0 mL) was slowly added 4-ethylphenylmagnesium bromide (39 mL, 0.5 M solution in THF) at 0° C., and the reaction mixture was stirred for 12 h at room temperature. The resulting mixture was quenched with sat. NH4Cl, diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide (5-bromo-2-(hydroxymethyl)phenyl)(4-ethylphenyl)methanol (146, 1.53 g, 49%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J=2.0 Hz, 1H), 7.42 (dd, J=8.0, 2.0 Hz, 1H), 7.26-7.17 (m, 5H), 5.97 (s, 1H), 4.58 (d, J=12.8 Hz, 1H), 4.43 (d, J=12.4 Hz, 1H), 2.65 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). at 0° C. The resulting mixture was quenched with sat. NH4Cl diluted with EtOAc washed with brine The organic layer was dried over MgSO4 filtered concentrated in vacuo The crude was purified by silica gel column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1) To a solution of 6-bromophthalide (144, 550 mg, 2.58 mmol) in dichloromethane (20.0 mL) was slowly added DIBAL-H (2.7 mL, 1.0 M solution in hexane) at −78° C., and the reaction mixture was stirred for 1.5 h at −78° C. The resulting mixture was quenched with sat. Na2SO4 and allowed to warm to room temperature. To the mixture was added anhydrous Na2SO4, and the mixture was stirred for 12 h, then filtered and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide 6-bromo-1,3-dihydroisobenzofuran-1-ol (145, 530 mg, 96%) as yellow oil. at −78° C. The resulting mixture was quenched with sat. Na2SO4 to warm to room temperature To the mixture was added anhydrous Na2SO4 the mixture was stirred for 12 h filtered concentrated in vacuo The crude was purified by silica gel column chromatography

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

Procedure: Step 2) To a solution of compound 145 (2.1 g, 9.77 mmol) in tetrahydrofuran (40.0 mL) was slowly added 4-ethylphenylmagnesium bromide (39 mL, 0.5 M solution in THF) at 0° C., and the reaction mixture was stirred for 12 h at room temperature. The resulting mixture was quenched with sat. NH4Cl, diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide (5-bromo-2-(hydroxymethyl)phenyl)(4-ethylphenyl)methanol (146, 1.53 g, 49%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J=2.0 Hz, 1H), 7.42 (dd, J=8.0, 2.0 Hz, 1H), 7.26-7.17 (m, 5H), 5.97 (s, 1H), 4.58 (d, J=12.8 Hz, 1H), 4.43 (d, J=12.4 Hz, 1H), 2.65 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). at 0° C. The resulting mixture was quenched with sat. NH4Cl diluted with EtOAc washed with brine The organic layer was dried over MgSO4 filtered concentrated in vacuo The crude was purified by silica gel column chromatography

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

Procedure: Step 2) To a solution of compound 145 (2.1 g, 9.77 mmol) in tetrahydrofuran (40.0 mL) was slowly added 4-ethylphenylmagnesium bromide (39 mL, 0.5M solution in THF) at 0° C., and the reaction mixture was stirred for 12 h at room temperature. The resulting mixture was quenched with sat. NH4Cl, diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide (5-bromo-2-(hydroxymethyl)phenyl)(4-ethylphenyl)methanol (146, 1.53 g, 49%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J=2.0 Hz, 1H), 7.42 (dd, J=8.0, 2.0 Hz, 1H), 7.26-7.17 (m, 5H), 5.97 (s, 1H), 4.58 (d, J=12.8 Hz, 1H), 4.43 (d, J=12.4 Hz, 1H), 2.65 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). at 0° C. The resulting mixture was quenched with sat. NH4Cl diluted with EtOAc washed with brine The organic layer was dried over MgSO4 filtered concentrated in vacuo The crude was purified by silica gel column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1) To a solution of 6-bromophthalide (144, 550 mg, 2.58 mmol) in dichloromethane (20.0 mL) was slowly added DIBAL-H (2.7 mL, 1.0M solution in hexane) at −78° C., and the reaction mixture was stirred for 1.5 h at −78° C. The resulting mixture was quenched with sat. Na2SO4 and allowed to warm to room temperature. To the mixture was added anhydrous Na2SO4, and the mixture was stirred for 12 h, then filtered and concentrated in vacuo. The crude was purified by silica gel column chromatography to provide 6-bromo-1,3-dihydroisobenzofuran-1-ol (145, 530 mg, 96%) as yellow oil. at −78° C. The resulting mixture was quenched with sat. Na2SO4 to warm to room temperature To the mixture was added anhydrous Na2SO4 the mixture was stirred for 12 h filtered concentrated in vacuo The crude was purified by silica gel column chromatography