4-bromo-2-fluoro-1-propan-2-ylbenzene

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: The title compound was prepared analogously to Example A(64), where 1-Bromo-3-ethyl-benzene was substituted in place of 4-bromo-2-fluoro-1-isopropylbenzene of that example and Enantiomer B of 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one was used in place of the racemic alkyne.

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

Procedure: The title compound was prepared analogously to Example A(64), where 1-Bromo-3-ethyl-benzene was substituted in place of 4-bromo-2-fluoro-1-isopropylbenzene of that example and Enantiomer B of 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one was used in place of the racemic alkyne.

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

Procedure: The title compound was prepared analogously to Example A(64), where 1-Bromo-3-ethyl-benzene was substituted in place of 4-bromo-2-fluoro-1-isopropylbenzene in that example, and Enantiomer A of 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one was used in place of the racemic alkyne.

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-fluoro-1-isopropylbenzene (5.0 g, 23.2 mmol), 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one (5.56 g, 21.0 mmol) were dissolved in anhydrous DMF (30 mL). To this solution, CuI (120 mg, 0.63 mmol), Pd(PPh3)2Cl2 (0.59 g, 0.84 mmol), and diisopropylamine (60 mL), were added sequentially. The mixture was then heated at 90° C. for 20 min before it was cooled down to 25° C. The reaction was diluted with EtOAc (150 mL) and washed with aqueous NH4Cl, brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (040% EtOAc in hexanes) to give the desired product (7.5 g, 81% yield). was cooled down to 25° C washed with aqueous NH4Cl, brine dried over Na2SO4 The solvent was removed in vacuo the residue was purified by flash column chromatography (040% EtOAc in hexanes)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-fluoro-1-isopropylbenzene (5.0 g, 23.2 mmol), 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one (5.56 g, 21.0 mmol) were dissolved in anhydrous DMF (30 mL). To this solution, CuI (120 mg, 0.63 mmol), Pd(PPh3)2Cl2 (0.59 g, 0.84 mmol), and diisopropylamine (60 mL), were added sequentially. The mixture was then heated at 90° C. for 20 min before it was cooled down to 25° C. The reaction was diluted with EtOAc (150 mL) and washed with aqueous NH4Cl, brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (040% EtOAc in hexanes) to give the desired product (7.5 g, 81% yield). was cooled down to 25° C washed with aqueous NH4Cl, brine dried over Na2SO4 The solvent was removed in vacuo the residue was purified by flash column chromatography (040% 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:0.00; pressure:0.00; stir:

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

Procedure: The title compound was prepared analogously to Example A(64), where 1-Bromo-3-ethyl-benzene was substituted in place of 4-bromo-2-fluoro-1-isopropylbenzene of that example and Enantiomer B of 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one was used in place of the racemic alkyne. 1H NMR (CDCl3): δ 1.23 (t, 3H, J=7.6 Hz), 1.50-1.83 (br m, 8H), 1.91-2.05 (m, 2H), 2.29 (m, 1H), 2.59-2.68 (m, 4H) 2.27, (s, 2H), 3.42 (s, 2H), 6.96 (m, 2H), 7.06 (d, 1H, J=7.01 Hz), 7.21 (t, 1H, J=8.0 Hz). ESIMS: MH+ 315.20, MH− 313.20.

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

Procedure: The title compound was prepared analogously to Example A(64), where 1-Bromo-3-ethyl-benzene was substituted in place of 4-bromo-2-fluoro-1-isopropylbenzene in that example, and Enantiomer A of 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one was used in place of the racemic alkyne. 1H NMR (CDCl3): δ 1.23 (t, 3H, J=7.6 Hz), 1.50-1.83 (br m, 8H), 1.91-2.05 (m, 2H), 2.29 (m, 1H), 2.59-2.68 (m, 4H) 2.27, (s, 2H), 3.42 (s, 2H), 6.96 (m, 2H), 7.06 (d, 1H, J=7.01 Hz), 7.21 (t, 1H, J=8.0 Hz). ESIMS: MH+ 315.20, MH− 313.20.

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-fluoro-1-isopropylbenzene (5.0 g, 23.2 mmol), 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one (5.56 g, 21.0 mmol) were dissolved in anhydrous DMF (30 mL). To this solution, CuI (120 mg, 0.63 mmol), Pd(PPh3)2Cl2 (0.59 g, 0.84 mmol), and diisopropylamine (60 mL), were added sequentially. The mixture was then heated at 90° C. for 20 min before it was cooled down to 25° C. The reaction was diluted with EtOAc (150 mL) and washed with aqueous NH4Cl, brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (0-40% EtOAc in hexanes) to give the desired product (7.5 g, 81% yield). 1H NMR (CDCl3, 300 MHz) δ: 1.22-1.28 (m, 8H), 1.69-1.74 (m, 10H), 1.80-1.86 (m, 2H), 2.19-2.26 (m, 1H), 2.62-2.70 (m, 2H), 3.18-3.25 (m, 1H), 5.46 (s, 1H), 7.00 (dd, J=10.61, 1.52 Hz, 1H), 7.09-7.11 (m, 1H), 7.18 (t, J=7.71 Hz, 1H). was cooled down to 25° C washed with aqueous NH4Cl, brine dried over Na2SO4 The solvent was removed in vacuo the residue was purified by flash column chromatography (0-40% EtOAc in hexanes)