2-(4-bromo-2-fluorophenyl)propan-2-ol

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 methyl 4-bromo-2-fluorobenzoate (12 g, 51.5 mmol) in anhydrous ether (140 mL) at 0° C. was added MeMgBr (3.0 M, 70 g) dropwise. The mixture was slowly warmed up to room temperature and stirred for 3 hours. The reaction was quenched by the addition of saturated NH4Cl and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (0–20% EtOAc in hexanes) to give the product (12 g, 95% yield). 1H NMR (300 MHz, CDCl3) δ: 1.62 (s, 6 H), 7.18–7.23 (m, 1 H), 7.25–7.28 (m, 1 H), 7.44–7.49 (m, 1 H). The reaction was quenched by the addition of saturated NH4Cl extracted with EtOAc (3×150 mL) The combined organic extracts were washed with brine dried with Na2SO4 evaporated to dryness The mixture was purified by flash column chromatography (0–20% EtOAc in hexanes)

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

Procedure: To a solution of methyl 4-bromo-2-fluorobenzoate (12 g, 51.5 mmol) in anhydrous ether (140 mL) at 0° C. was added MeMgBr (3.0 M, 70 g) dropwise. The mixture was slowly warmed up to room temperature and stirred for 3 hours. The reaction was quenched by the addition of saturated NH4Cl and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (0–20% EtOAc in hexanes) to give the product (12 g, 95% yield). 1H NMR (300 MHz, CDCl3) δ: 1.62 (s, 6 H), 7.18–7.23 (m, 1 H), 7.25–7.28 (m, 1 H), 7.44–7.49 (m, 1 H). The reaction was quenched by the addition of saturated NH4Cl extracted with EtOAc (3×150 mL) The combined organic extracts were washed with brine dried with Na2SO4 evaporated to dryness The mixture was purified by flash column chromatography (0–20% EtOAc in hexanes)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-fluorophenyl)propan-2-ol (5.8 g, 25.0 mmol) in anhydrous NMP (63 mL) was added 1-Cyclopentyl-2-propen-1-ol (3.15 g, 25.0 mmol), NaHCO3 (4.2 g, 50 mmol) and PdCl2(PPh3)2 (350 mg, 2 mol %). The mixture was heated to 140° C. for 4 hours before it was cooled down to room temperature. The reaction was diluted with aqueous NH4Cl, extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (10–50% EtOAc in hexanes) to give the product (2.5 g, 36% yield). 1H NMR (300 MHz, CDCl3) δ: 1.56–1.82 (m, 8 H), 1.62 (s, 6 H), 2.74–2.78 (m, 2 H), 2.82–2.89 (m, 2 H), 6.84–6.88 (m, 1 H), 6.93–6.95 (m, 1 H), 7.40–7.44 (m, 1 H). was cooled down to room temperature extracted with EtOAc (3×50 mL) The combined organic extracts were washed with brine dried with Na2SO4 evaporated to dryness The mixture was purified by flash column chromatography (10–50% EtOAc in hexanes)

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

Procedure: To a solution of 2-(4-bromo-2-fluorophenyl)propan-2-ol (7.6 g, 32.8 mmol) dissolved in anhydrous CH2Cl2 (300 mL) at 25° C. was added triethylsilane (7.8 mL, 49.1 mmol), followed by trifluoroacetic acid (25 mL, 328 mmol). The resulting solution was stirred at that temperature for 45 min. The solvent was removed in vacuo and the residue was purified by flash column chromatography (0–10% EtOAc in hexanes) to give the desired product (5.7 g, 80% yield). The solvent was removed in vacuo the residue was purified by flash column chromatography (0–10% EtOAc in hexanes)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-bromo-2-fluorobenzoate (8.0 g, 34.3 mmol) in anhydrous Et2O (85 mL) was treated with MeMgBr (3.0 M in THF, 30 mL). The resulting solution was stirred at 25° C. for 3 hours before it was quenched by the addition of H2O (10 mL). The mixture was extracted with EtOAc (50 mL) three times and the combined organic extracts were washed with aqueous NH4Cl, brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (0–25% EtOAc in hexanes) to give the desired product (7.2 g, 91% yield). was quenched by the addition of H2O (10 mL) The mixture was extracted with EtOAc (50 mL) three times the combined organic extracts were washed with aqueous NH4Cl, brine dried over Na2SO4 The solvent was removed in vacuo the residue was purified by flash column chromatography (0–25% EtOAc in hexanes)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-bromo-2-fluorobenzoate (8.0 g, 34.3 mmol) in anhydrous Et2O (85 mL) was treated with MeMgBr (3.0 M in THF, 30 mL). The resulting solution was stirred at 25° C. for 3 hours before it was quenched by the addition of H2O (10 mL). The mixture was extracted with EtOAc (50 mL) three times and the combined organic extracts were washed with aqueous NH4Cl, brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (0–25% EtOAc in hexanes) to give the desired product (7.2 g, 91% yield). was quenched by the addition of H2O (10 mL) The mixture was extracted with EtOAc (50 mL) three times the combined organic extracts were washed with aqueous NH4Cl, brine dried over Na2SO4 The solvent was removed in vacuo the residue was purified by flash column chromatography (0–25% EtOAc in hexanes)

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

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

Procedure: To a stirred solution of 2-(4-bromo-2-fluoro-phenyl)-propan-2-ol (18.5 g, 79.4 mmol) and 3,4-dihydro-2H-pyran (10.9 mL, 119.1 mmol) in dichloromethane (165 mL) was added pyridinium-p-toluene sulfonate (2 g, 7.91 mmol) at room temperature. The resulting mixture was stirred at room temperature for 12 h, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 25% ethyl acetate/hexanes) to afford 2-[1-(4-bromo-2-fluoro-phenyl)-1-methyl-ethoxy]-tetrahydro-pyran (9.7 g, 38.6%) as a light yellow oil. extracted with ethyl acetate washed with brine dried over anhydrous sodium sulfate The solvent was evaporated in vacuo the residue was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 25% ethyl acetate/hexanes)

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

Procedure: To a solution of methyl 4-bromo-2-fluorobenzoate (12 g, 51.5 mmol) in anhydrous ether (140 mL) at 0° C. was added MeMgBr (3.0 M, 70 g) dropwise. The mixture was slowly warmed up to room temperature and stirred for 3 hours. The reaction was quenched by the addition of saturated NH4Cl and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (0-20% EtOAc in hexanes) to give the product (12 g, 95% yield). 1H NMR (300 MHz, CDCl3) δ: 1.62 (s, 6H), 7.18-7.23 (m, 1H), 7.25-7.28 (m, 1H), 7.44-7.49 (m, 1H). The reaction was quenched by the addition of saturated NH4Cl extracted with EtOAc (3×150 mL) The combined organic extracts were washed with brine dried with Na2SO4 evaporated to dryness The mixture was purified by flash column chromatography (0-20% EtOAc in hexanes)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-fluorophenyl)propan-2-ol (5.8 g, 25.0 mmol) in anhydrous NMP (63 mL) was added 1-Cyclopentyl-2-propen-1-ol (3.15 g, 25.0 mmol), NaHCO3 (4.2 g, 50 mmol) and PdCl2(PPh3)2 (350 mg, 2 mol %). The mixture was heated to 140° C. for 4 hours before it was cooled down to room temperature. The reaction was diluted with aqueous NH4Cl, extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (10-50% EtOAc in hexanes) to give the product (2.5 g, 36% yield). 1H NMR (300 MHz, CDCl3) δ: 1.56-1.82 (m, 8H), 1.62 (s, 6H), 2.74-2.78 (m, 2H), 2.82-2.89 (m, 2H), 6.84-6.88 (m, 1H), 6.93-6.95 (m, 1H), 7.40-7.44 (m, 1H). was cooled down to room temperature extracted with EtOAc (3×50 mL) The combined organic extracts were washed with brine dried with Na2SO4 evaporated to dryness The mixture was purified by flash column chromatography (10-50% EtOAc in hexanes)

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

Procedure: To a solution of 2-(4-bromo-2-fluorophenyl)propan-2-ol (7.6 g, 32.8 mmol) dissolved in anhydrous CH2Cl2 (300 mL) at 25° C. was added triethylsilane (7.8 mL, 49.1 mmol), followed by trifluoroacetic acid (25 mL, 328 mmol). The resulting solution was stirred at that temperature for 45 min. The solvent was removed in vacuo and the residue was purified by flash column chromatography (0-10% EtOAc in hexanes) to give the desired product (5.7 g, 80% yield). 1H NMR (CDCl3, 400 MHz) δ: 1.23 (d, J=6.82 Hz, 3H), 3.15-3.22 (m, 1H), 7.11 (t, J=8.08 Hz, 1H), 7.17 (dd, J=9.85, 1.77 Hz, 1H), 7.22 (d, J=8.34 Hz, 1H). The solvent was removed in vacuo the residue was purified by flash column chromatography (0-10% EtOAc in hexanes)