(3-chloro-2-propan-2-yloxyphenyl)methanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Diisobutylaluminum lithium hydride (26.8 mL of a 1.0 M in hexanes, 26.8 mmol) was added dropwise to a solution of 3-chloro-2-isopropoxybenzoic acid isopropyl ester (2.29 g, 8.94 mmol) in THF (20 mL) under N2 at 0° C. After the addition was complete, the ice bath was removed, the solution warmed to ambient temperature, and the reaction mixture stirred for 5 d. The reaction was cooled to 0° C. and quenched using 1N HCl (100 mL) until all the solids dissolved. The solution was extracted with Et2O (3×50 mL). The combined organics were washed with brine (2×100 mL), dried (Na2SO4) and concentrated to yield the title compound (1.60 g, 89%) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 7.41 (d, J=4.5 Hz, 1H), 7.33 (dd, J=8.0, 1.5 Hz, 1H), 7.11 (t, J=8.0 Hz, 1H), 5.19 (t, J=5.7 Hz, 1H), 4.53 (d, J=5.5 Hz, 1H), 4.44-4.36 (m, 1H), 1.24 (d, J=6.1 Hz, 6H). After the addition the ice bath was removed The reaction was cooled to 0° C. quenched dissolved The solution was extracted with Et2O (3×50 mL) The combined organics were washed with brine (2×100 mL) dried (Na2SO4) concentrated

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

Procedure: MnO2 (4.86 g, 56.0 mmol) was added to a stirring solution of (3-chloro-2-isopropoxyphenyl)methanol (1.60 g, 8.00 mmol) in benzene (75 mL), under N2. After stirring for 48 h, the solution was filtered over diatomaceous earth, the pad was rinsed with CH2Cl2 (100 mL), and the solution was concentrated to a yellow oil. Purification by column chromatography (silica gel hexanes/EtOAc, 98:2) gave the title compound (0.50 g, 31%) as a clear oil: 1H NMR (300 MHz, DMSO-d6) δ 10.28 (s, 1H), 7.84 (dd, J=7.8, 1.5 Hz, 1H), 7.72 (dd, J=7.8, 1.5 Hz, 1H), 7.31 (t, J=8.1 Hz, 1H), 4.53-4.48 (m, 1H), 1.32 (d, J=6.0 Hz, 6H). the solution was filtered over diatomaceous earth the pad was rinsed with CH2Cl2 (100 mL) the solution was concentrated to a yellow oil Purification by column chromatography (silica gel hexanes/EtOAc, 98:2)

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

Procedure: MnO2 (4.86 g, 56.0 mmol) was added to a stirring solution of (3-chloro-2-isopropoxyphenyl)methanol (1.60 g, 8.00 mmol) in benzene (75 mL), under N2. After stirring for 48 h, the solution was filtered over diatomaceous earth, the pad was rinsed with CH2Cl2 (100 mL), and the solution was concentrated to a yellow oil. Purification by column chromatography (silica gel hexanes/EtOAc, 98:2) gave the title compound (0.50 g, 31%) as a clear oil: 1H NMR (300 MHz, DMSO-d6) δ 10.28 (s, 1H), 7.84 (dd, J=7.8, 1.5 Hz, 1H), 7.72 (dd, J=7.8, 1.5 Hz, 1H), 7.31 (t, J=8.1 Hz, 1H), 4.53-4.48 (m, 1H), 1.32 (d, J=6.0 Hz, 6H). the solution was filtered over diatomaceous earth the pad was rinsed with CH2Cl2 (100 mL) the solution was concentrated to a yellow oil Purification by column chromatography (silica gel hexanes/EtOAc, 98:2)

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

Procedure: Diisobutylaluminum lithium hydride (26.8 mL of a 1.0 M in hexanes, 26.8 mmol) was added dropwise to a solution of 3-chloro-2-isopropoxybenzoic acid isopropyl ester (2.29 g, 8.94 mmol) in THF (20 mL) under N2 at 0° C. After the addition was complete, the ice bath was removed, the solution warmed to ambient temperature, and the reaction mixture stirred for 5 d. The reaction was cooled to 0° C. and quenched using 1N HCl (100 mL) until all the solids dissolved. The solution was extracted with Et2O (3×50 mL). The combined organics were washed with brine (2×100 mL), dried (Na2SO4) and concentrated to yield the title compound (1.60 g, 89%) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 7.41 (d, J=4.5 Hz, 1H), 7.33 (dd, J=8.0, 1.5 Hz, 1H), 7.11 (t, J=8.0 Hz, 1H), 5.19 (t, J=5.7 Hz, 1H), 4.53 (d, J=5.5 Hz, 1H), 4.44-4.36 (m, 1H), 1.24 (d, J=6.1 Hz, 6H). After the addition the ice bath was removed The reaction was cooled to 0° C. quenched dissolved The solution was extracted with Et2O (3×50 mL) The combined organics were washed with brine (2×100 mL) dried (Na2SO4) concentrated