(4-bromophenyl)-phenylmethanol

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 11 (1 g, 3.80 mmol) and 4-fluorophenyl boronic acid (585 mg, 4.18 mmol) in a 2:1 mixture of DME:water (30 mL), was added Pd(PPh3)4 (307 mg, 0.27 mmol), tri-o-toly phosphine (81 mg, 0.27 mmol) and potassium carbonate (2.63 g, 19.0 mmol). The solution was heated to 80° C. and stirred for 16 hours. Then water (50 mL) was added and the organic residue was extracted with ethyl acetate (2×40 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified via prep-HPLC (ISCO) in silica gel column with a gradient of ethyl acetate (2-50%) in hexane to afford compound 12 as a white solid (600 mg, 57%). 1H NMR (DMSO-d6) δ (ppm): 7.67-7.63 (m, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.45-7.38 (m, 4H), 7.32-7.17 (m, 5H), 5.93 (d, J=3.9 Hz, 1H), 5.73 (d, J=3.8 Hz, 1H). the organic residue was extracted with ethyl acetate (2×40 mL) The organic layer was dried over Na2SO4 filtered concentrated The residue was purified via prep-HPLC (ISCO) in silica gel column with a gradient of ethyl acetate (2-50%) in hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 11 (1 g, 3.80 mmol) and 4-fluorophenyl boronic acid (585 mg, 4.18 mmol) in a 2:1 mixture of DME:water (30 mL), was added Pd(PPh3)4 (307 mg, 0.27 mmol), tri-o-toly phosphine (81 mg, 0.27 mmol) and potassium carbonate (2.63 g, 19.0 mmol). The solution was heated to 80° C. and stirred for 16 hours. Then water (50 mL) was added and the organic residue was extracted with ethyl acetate (2×40 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified via prep-HPLC (ISCO) in silica gel column with a gradient of ethyl acetate (2-50%) in hexane to afford compound 12 as a white solid (600 mg, 57%). 1H NMR (DMSO-d6) δ (ppm): 7.67-7.63 (m, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.45-7.38 (m, 4H), 7.32-7.17 (m, 5H), 5.93 (d, J=3.9 Hz, 1H), 5.73 (d, J=3.8 Hz, 1H). the organic residue was extracted with ethyl acetate (2×40 mL) The organic layer was dried over Na2SO4 filtered concentrated The residue was purified via prep-HPLC (ISCO) in silica gel column with a gradient of ethyl acetate (2-50%) in hexane

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

Procedure: To a solution of p-bromobenzaldehyde 10 (4 g, 21.6 mmol) in THF (20 mL) was added phenyl magnesium bromide (22.7 mL, 22.7 mmol) and the reaction mixture was stirred at room temperature for 30 minutes, quenched with water and partially concentrated under vacuum. The crude material was dissolved in ethyl acetate and washed with water. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The residue was purified via prep-HPLC (ISCO) in silica gel column with a gradient of ethyl acetate (5-45%) in hexanes to afford title compound 11 as a colorless oil (3.7 g, 65%). 1H NMR (DMSO-d6) δ (ppm): 7.49-7.45 (m, 2H), 7.36-7.17 (m, 7H), 5.98 (d, J=4.1 Hz, 1H), 5.68 (d, J=3.9 Hz, 1H). quenched with water partially concentrated under vacuum The crude material was dissolved in ethyl acetate washed with water The organic layer was separated dried over Na2SO4 filtered concentrated The residue was purified via prep-HPLC (ISCO) in silica gel column with a gradient of ethyl acetate (5-45%) in hexanes

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: In a similar manner to Preparation 14, Step 2, the reaction of (4-bromophenyl)(phenyl)methanol (10 g, 38 mmol), and (1-methoxy-2-methylprop-1-enyloxy)trimethylsilane (23.2 g, 133 mmol) in the presence of titanium tetrachloride (1M in DCM, 42 ml. 41.8 mmol) afforded methyl 3-(4-bromophenyl)-2,2-dimethyl-3-phenylpropanoate (13 g, 99% yield). LC/MS (m/z) 347.05, 349 [(M+1)+]; HPLC Rt: 4.18 min. In a similar manner to Preparation 14, Step 2

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

Procedure: α,α′-Diphenyl-α-hydroxyl-p-xylene was prepared as shown in Scheme 4 by using 29.0 g (117 mmol) of 4-bromo diphenylmethane and 11.2 g (106 mmol) of benzaldehyde/19.7 g (106 mmol) by the similar procedure to the method for preparing 4-bromobenzhydrol. The crude product was dissolved in chloroform and filtered through G60 column filled with silica gel. After evaporating the solvent, the result product was recrystallized with hexane/chloroform (9:1 v/v) to provide a yield of 86%. MP: 64° C. filtered through G60 column filled with silica gel After evaporating the solvent the result product was recrystallized with hexane/chloroform (9:1 v/v) to provide a yield of 86%

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromodiphenylmethane was prepared as shown in Scheme 3. 4-Bromobenzhydrol in a 3-neck flask equipped with a reflux condenser and a thermometer was mixed with 500 ml of acetic acid, 113 g (445 mmol) of iodine and 226 ml, 50 wt. % of phosphorous acid (2.2 mol). The reaction mixture was heated at 80° C. for 24 hours and then cooled. 700 ml of ice-water was added to the reaction mixture and the reaction mixture was extracted with hexane (200 ml) 5 times. The combined organic layer was washed with 10 wt. % KOH solution and 200 ml of a saturated ammonium chloride solution and then further washed with a saturated Na2SO3 solution twice. The solvent was evaporated and the result product was dried under vacuum to provide a yield of 61% (276 mmol). BP: 103° C. (5*10−2 mbar) cooled the reaction mixture was extracted with hexane (200 ml) 5 times The combined organic layer was washed with 10 wt. % KOH solution and 200 ml of a saturated ammonium chloride solution further washed with a saturated Na2SO3 solution twice The solvent was evaporated the result product was dried under vacuum to provide a yield of 61% (276 mmol)