2-(4-bromophenyl)propan-2-ol

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:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Bromophenyl)ethanone (9.25 g, 46.5 mmol) was dissolved in tetrahydrofuran (200 mL). The solution was cooled in a −50° C. bath. Methylmagnesium bromide (3M in ether, 46.5 mL, 139 mmol) was added over a 15 min period. The reaction was allowed to warm to room temperature and then stirred for 20 h. The reaction was quenched with saturated ammonium chloride and then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated to give an oil. The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes) to give the product a colorless oil (9.1 g, 46.2 mmol, 91% yield). MS (ESI) m/z 197.1 [M]+, 199.1 [M+2]+. to warm to room temperature The reaction was quenched with saturated ammonium chloride extracted with ethyl acetate The organic layer was dried over magnesium sulfate filtered concentrated to give an oil The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes)

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Bromophenyl)ethanone (9.25 g, 46.5 mmol) was dissolved in tetrahydrofuran (200 mL). The solution was cooled in a −50° C. bath. Methylmagnesium bromide (3M in ether, 46.5 mL, 139 mmol) was added over a 15 min period. The reaction was allowed to warm to room temperature and then stirred for 20 h. The reaction was quenched with saturated ammonium chloride and then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated to give an oil. The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes) to give the product a colorless oil (9.1 g, 46.2 mmol, 91% yield). MS (ESI) m/z 197.1 [M]+, 199.1 [M+2]+. to warm to room temperature The reaction was quenched with saturated ammonium chloride extracted with ethyl acetate The organic layer was dried over magnesium sulfate filtered concentrated to give an oil The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes)

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

Procedure: A mixture of 6.87 g of ethyl 4-bromobenzoate (10) was allowed to react with 64 mL (1.4 M in toluene) of methyl magnesium bromide in THF at −40° C. for 1 hour, and the reaction mixture was gradually warmed to 0° C. The reaction was quenched with saturated aqueous ammonium chloride solution and the resultant mixture was extracted with ethyl acetate. The organic layer was washed with brine, was dried over magnesium sulfate, was filtered, and the solvent was removed in vacuo. Purification by silica gel chromatography (50:1 to 10:1 hexanes-ethyl acetate) afforded 6.44 g (99% yield) of 2-(4-bromophenyl)propan-2-o1; MS (AP/CI) observed: 199.1 (M+H−H2O)+, 100%; 213.1, 215.1 (M−H)−, 60%, 80%. 2-(4-Bromophenyl)propan-2-o1 (1.77 g) and iodomethane (1.16 g) in THF (100 mL) were treated with sodium hydride, 60% in mineral oil (328 mg). After stirring for 24 h at room temperature, the reaction mixture was quenched with dilute aqueous hydrochloric acid, was extracted with ethyl acetate, and the organic layer was washed with brine, was dried over magnesium sulfate, was filtered, and the solvent was removed in vacuo. The resultant oil was purified by silica gel chromatography (200:1 hexanes-ethylacetate) to afford 0.5 g of 1-bromo-4-(1-methoxy-1-methyl-ethyl)-benzene; 13C NMR (400 MHz, CDCl3) δ 145.35, 131.53, 127.91, 121.00, 50.90, 28.60. the reaction mixture was quenched with dilute aqueous hydrochloric acid was extracted with ethyl acetate the organic layer was washed with brine was dried over magnesium sulfate was filtered the solvent was removed in vacuo The resultant oil was purified by silica gel chromatography (200:1 hexanes-ethylacetate)

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Bromophenyl)ethanone (9.25 g, 46.5 mmol) was dissolved in tetrahydrofuran (200 mL). The solution was cooled in a −50° C. bath. Methylmagnesium bromide (3M in ether, 46.5 mL, 139 mmol) was added over a 15 min period. The reaction was allowed to warm to room temperature and then stirred for 20 h. The reaction was quenched with saturated ammonium chloride and then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated to give an oil. The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes) to give the product a colorless oil (9.1 g, 46.2 mmol, 91% yield). MS (ESI) m/z 197.1 [M]+, 199.1 [M+2]+. to warm to room temperature The reaction was quenched with saturated ammonium chloride extracted with ethyl acetate The organic layer was dried over magnesium sulfate filtered concentrated to give an oil The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes)

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(4-Bromophenyl)ethanone (9.25 g, 46.5 mmol) was dissolved in tetrahydrofuran (200 mL). The solution was cooled in a −50° C. bath. Methylmagnesium bromide (3M in ether, 46.5 mL, 139 mmol) was added over a 15 min period. The reaction was allowed to warm to room temperature and then stirred for 20 h. The reaction was quenched with saturated ammonium chloride and then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated to give an oil. The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes) to give the product a colorless oil (9.1 g, 46.2 mmol, 91% yield). MS (ESI) m/z 197.1 [M]+, 199.1 [M+2]+. to warm to room temperature The reaction was quenched with saturated ammonium chloride extracted with ethyl acetate The organic layer was dried over magnesium sulfate filtered concentrated to give an oil The oil was purified on a silica gel column (0-20% ethyl acetate in hexanes)

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

Procedure: N-trimethylsilylimidazole (80.6 mL, 0.552 mol) was added to a solution of the crude 2-(4-bromo-phenyl)-propan-2-ol in tetrahydrofuran (500 mL) in a nitrogen atmosphere at room temperature, and the mixture was stirred at the same temperature overnight. The reaction mixture was poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was distilled off under reduced pressure. The resulting residue was subjected to silica gel chromatography (n-hexane:ethyl acetate=40:1) to give the title compound as a colorless oil (125.6 g, 87% in two steps). followed by extraction with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate filtered the solvent was distilled off under reduced pressure

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

Procedure: Methyllithium (1.10 mol/l solution in diethyl ether, 502 mL, 0.552 mol) was added to a solution of 4-bromoacetophenone (100 g, 0.502 mol) in tetrahydrofuran (500 mL) in a nitrogen atmosphere at −78° C., and the mixture was stirred at the same temperature for one hour. The reaction mixture was poured into a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give crude 2-(4-bromo-phenyl)-propan-2-ol. followed by extraction with ethyl acetate The extract was washed with brine dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure

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

Procedure: 2-(4-Bromophenyl)propan-2-ol and 8-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-2-amine are reacted under Buchwald Hartwig conditions as described in general procedure 2.

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

Procedure: The title compound was prepared from the reaction of 5-methyl-2-((S)-1-(4-fluorophenyl)ethylamino)thiazol-4(5H)-one with 2-(4-bromophenyl)propan-2-ol using the procedure described for 2a. 4.0 equivalents of LiN(SiMe3)2 was used. MS (ESI, pos. ion) m/z: 387 (M+1).