(4-bromo-2-ethylphenyl)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:

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

Procedure: To a solution of (4-bromo-2-ethylphenyl)methanol (CAS 877131-21-0) (2.8 g, 13 mmol) in methylene chloride (45 mL) were added pyridinium p-toluenesulfonate (327 mg, 1.3 mmol) and 3,4-dihydro-2H-pyran (2.4 mL, 26 mmol) and stirred at RT for 16 h. The reaction mixture was diluted with water, extracted with methylene chloride, dried with magnesium sulfate and concentrated. Purification by MPLC (30% ethyl acetate in hexanes) afforded 2.9 g of Intermediate 1 as a colorless oil. extracted with methylene chloride dried with magnesium sulfate concentrated Purification by MPLC (30% ethyl acetate in hexanes)

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

Procedure: To a solution of (4-bromo-2-ethylphenyl)methanol (CAS 877131-21-0) (2.8 g, 13 mmol) in methylene chloride (45 mL) were added pyridinium p-toluenesulfonate (327 mg, 1.3 mmol) and 3,4-dihydro-2H-pyran (2.4 mL, 26 mmol) and stirred at RT for 16 h. The reaction mixture was diluted with water, extracted with methylene chloride, dried with magnesium sulfate and concentrated. Purification by MPLC (30% ethyl acetate in hexanes) afforded 2.9 g of Intermediate 1 as a colorless oil. extracted with methylene chloride dried with magnesium sulfate concentrated Purification by MPLC (30% ethyl acetate in hexanes)

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

Procedure: Morpholine-N-oxide (5.0 g, 43 mmol) was stirred in dichloromethane (30 mL) over 3A sieves 30 min under N2 atmosphere. (4-Bromo-2-ethyl-phenyl)-methanol (3.1 g, 14.4 mmol), then tetrapropylammonium perruthenate (250 mg, 0.72 mmol) was added. The solution was stirred 2 h then filtered through a plug of silica. The silica was washed with 30% ethyl acetate in hexanes, and the organics were pooled. The solution was concentrated in vacuo to give a light yellow oil (3.4 g). then filtered through a plug of silica The silica was washed with 30% ethyl acetate in hexanes The solution was concentrated in vacuo

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

Procedure: To a solution of (4-bromo-2-ethyl-phenyl)-methanol (0.700 g, 3.25 mmol) in DMF (30 mL) was added NaH (0.156 g, 60% dispersion in mineral oil, 3.90 mmol) followed by Mel (0.22 mL, 3.58 mmol). The mixture was stirred for 16 hours and then partitioned between H2O and EtOAc. The aqueous layer was extracted with EtOAc, and the organic layer was washed with brine, dried over Na2SO4, and concentrated to a yellow oil. Purification by flash column chromatography (0% to 4% EtOAc in hexanes) gave the product as a clear oil (0.51 g, 69%). 1H NMR (300 MHz, CDCl3): δ 1.15 (t, J=7.6 Hz, 3 H), 2.58 (q, J=7.5 Hz, 2 H), 3.32 (s, 3 H), 4.35 (s, 2 H), 7.12 (m, 1 H), 7.24 (m, 1 H), 7.27 (d, J=2.1 Hz, 1 H). partitioned between H2O and EtOAc The aqueous layer was extracted with EtOAc the organic layer was washed with brine dried over Na2SO4 concentrated to a yellow oil Purification by flash column chromatography (0% to 4% EtOAc in hexanes)

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

Procedure: To a solution of (4-bromo-2-ethyl-phenyl)-methanol (0.700 g, 3.25 mmol) in DMF (30 mL) was added NaH (0.156 g, 60% dispersion in mineral oil, 3.90 mmol) followed by Mel (0.22 mL, 3.58 mmol). The mixture was stirred for 16 hours and then partitioned between H2O and EtOAc. The aqueous layer was extracted with EtOAc, and the organic layer was washed with brine, dried over Na2SO4, and concentrated to a yellow oil. Purification by flash column chromatography (0% to 4% EtOAc in hexanes) gave the product as a clear oil (0.51 g, 69%). 1H NMR (300 MHz, CDCl3): δ 1.15 (t, J=7.6 Hz, 3 H), 2.58 (q, J=7.5 Hz, 2 H), 3.32 (s, 3 H), 4.35 (s, 2 H), 7.12 (m, 1 H), 7.24 (m, 1 H), 7.27 (d, J=2.1 Hz, 1 H). partitioned between H2O and EtOAc The aqueous layer was extracted with EtOAc the organic layer was washed with brine dried over Na2SO4 concentrated to a yellow oil Purification by flash column chromatography (0% to 4% EtOAc in hexanes)

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

Procedure: To a solution of (4-bromo-2-ethyl-phenyl)-methanol (7.9 g, 36.7 mmol) in anhydrous CHCl3 (122 mL) was added PBr3(4.2 mL, 44.1 mmol). The resulting mixture was stirred at room temperature for 2 hours before it was quenched by the addition of water. The organic layer was washed with NaHCO3, brine and dried over MgSO4. The solvent was removed in vacuo and the residue was filtered through a pad of silica gel with 20% EtOAc in hexanes. The solvent was removed in vacuo to afford the desired product (8.4 g, 83%). 1H NMR (300 MHz, CDCl3): δ 1.29 (t, J=7.5 Hz, 3 H), 2.71–2.78 (m, 2 H), 4.48 (s, 2H), 7.17–7.20 (m, 1H), 7.29–7.32 (m, 1 H), 7.36–7.38 (m, 1H). was quenched by the addition of water The organic layer was washed with NaHCO3, brine dried over MgSO4 The solvent was removed in vacuo the residue was filtered through a pad of silica gel with 20% EtOAc in hexanes The solvent was removed in vacuo

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

Procedure: To a solution of 4-bromo-2-ethyl-benzoic acid (115 mmol) in anhydrous THF (380 mL) at 0° C. was added BH3.THF complex (1.0 N solution in THF, 230 mL) over 30 min. The resulting mixture was slowly warmed up to room temperature and the stirred for 15 hours. The reaction was carefully quenched with slow addition of water. The solvent was removed and the residue was taken up in EtOAc. The organic layer was washed with 1.0 N HCl, H2O, brine and dried over MgSO4. The solvent was removed to afford the desired product. (22 g, 89% yield). 1H NMR (300 MHz, CDCl3): δ 1.23 (t, J=7.5 Hz, 3 H), 2.64–3.01 (m, 2H), 4.68 (s, 2H), 7.24–7.26 (m, 1H), 7.32–7.36 (m, 2H). The reaction was carefully quenched with slow addition of water The solvent was removed The organic layer was washed with 1.0 N HCl, H2O, brine dried over MgSO4 The solvent was removed

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

Procedure: To a solution of 4-bromo-2-ethyl-benzoic acid (115 mmol) in anhydrous THF (380 mL) at 0° C. was added BH3.THF complex (1.0 N solution in THF, 230 mL) over 30 min. The resulting mixture was slowly warmed up to room temperature and the stirred for 15 hours. The reaction was carefully quenched with slow addition of water. The solvent was removed and the residue was taken up in EtOAc. The organic layer was washed with 1.0 N HCl, H2O, brine and dried over MgSO4. The solvent was removed to afford the desired product. (22 g, 89% yield). 1H NMR (300 MHz, CDCl3): δ 1.23 (t, J=7.5 Hz, 3 H), 2.64–3.01 (m, 2H), 4.68 (s, 2H), 7.24–7.26 (m, 1H), 7.32–7.36 (m, 2H). The reaction was carefully quenched with slow addition of water The solvent was removed The organic layer was washed with 1.0 N HCl, H2O, brine dried over MgSO4 The solvent was removed

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