1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol

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 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. solution of 4-bromo-2-fluorobenzaldehyde (1.00 g, 4.93 mmol) in tetrahydrofuran (50 mL) was added trimethylsilyl trifluoromethane (0.77 mL, 4.9 mmol) dropwise over 5 minutes. The reaction was stirred at 0° C. for 10 minutes. Then tetrabutylammonium fluoride (0.49 mL, 0.49 mmol, 1 M in tetrahydrofuran) was slowly added and the reaction was allowed to gradually warm to room temperature and stir for 3 days. The reaction was concentrated and the residue was taken up in dichloromethane. The solution was washed once with 1 N aqueous hydrochloric acid and once with brine. The organics were dried over magnesium sulfate, filtered, and concentrated. Purification by column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (1.0 g, 75%) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 7.48 (d, J=7.61 Hz, 1H), 7.39 (d, J=1.76 Hz, 1H), 7.29 (dd, J=9.56, 1.95 Hz, 1H), 5.33-5.40 (m, 1H), 2.70 (d, J=5.46 Hz, 1H). to gradually warm to room temperature stir for 3 days The reaction was concentrated The solution was washed once with 1 N aqueous hydrochloric acid and once with brine The organics were dried over magnesium sulfate filtered concentrated Purification by column chromatography (0-50% ethyl acetate/heptanes)

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

Procedure: To a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

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

Procedure: To a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. solution of 4-bromo-2-fluorobenzaldehyde (1.00 g, 4.93 mmol) in tetrahydrofuran (50 mL) was added trimethylsilyl trifluoromethane (0.77 mL, 4.9 mmol) dropwise over 5 minutes. The reaction was stirred at 0° C. for 10 minutes. Then tetrabutylammonium fluoride (0.49 mL, 0.49 mmol, 1 M in tetrahydrofuran) was slowly added and the reaction was allowed to gradually warm to room temperature and stir for 3 days. The reaction was concentrated and the residue was taken up in dichloromethane. The solution was washed once with 1 N aqueous hydrochloric acid and once with brine. The organics were dried over magnesium sulfate, filtered, and concentrated. Purification by column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (1.0 g, 75%) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 7.48 (d, J=7.61 Hz, 1H), 7.39 (d, J=1.76 Hz, 1H), 7.29 (dd, J=9.56, 1.95 Hz, 1H), 5.33-5.40 (m, 1H), 2.70 (d, J=5.46 Hz, 1H). to gradually warm to room temperature stir for 3 days The reaction was concentrated The solution was washed once with 1 N aqueous hydrochloric acid and once with brine The organics were dried over magnesium sulfate filtered concentrated Purification by column chromatography (0-50% ethyl acetate/heptanes)

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

Procedure: To a solution of 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol (1.09 g, 3.99 mmol) in ethyl acetate (30 mL) was added 2-iodoxybenzoic acid (2.28 g, 7.97 mmol). The reaction was heated to reflux overnight. The reaction was cooled to room temperature and diluted with heptanes (30 mL). The mixture was filtered through Celite and the filtrate was concentrated to give the title compound (1.03 g, 95%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3, δ): 7.44 (dd, J=10.15, 1.56 Hz, 1H), 7.48 (m, 1H), 7.76 (m, 1H). The reaction was heated to reflux overnight The mixture was filtered through Celite the filtrate was concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. solution of 4-bromo-2-fluorobenzaldehyde (1.00 g, 4.93 mmol) in tetrahydrofuran (50 mL) was added trimethylsilyl trifluoromethane (0.77 mL, 4.9 mmol) dropwise over 5 minutes. The reaction was stirred at 0° C. for 10 minutes. Then tetrabutylammonium fluoride (0.49 mL, 0.49 mmol, 1 M in tetrahydrofuran) was slowly added and the reaction was allowed to gradually warm to room temperature and stir for 3 days. The reaction was concentrated and the residue was taken up in dichloromethane. The solution was washed once with 1 N aqueous hydrochloric acid and once with brine. The organics were dried over magnesium sulfate, filtered, and concentrated. Purification by column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (1.0 g, 75%) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 7.48 (d, J=7.61 Hz, 1H), 7.39 (d, J=1.76 Hz, 1H), 7.29 (dd, J=9.56, 1.95 Hz, 1H), 5.33-5.40 (m, 1H), 2.70 (d, J=5.46 Hz, 1H). to gradually warm to room temperature stir for 3 days The reaction was concentrated The solution was washed once with 1 N aqueous hydrochloric acid and once with brine The organics were dried over magnesium sulfate filtered concentrated Purification by column chromatography (0-50% ethyl acetate/heptanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. solution of 4-bromo-2-fluorobenzaldehyde (1.00 g, 4.93 mmol) in tetrahydrofuran (50 mL) was added trimethylsilyl trifluoromethane (0.77 mL, 4.9 mmol) dropwise over 5 minutes. The reaction was stirred at 0° C. for 10 minutes. Then tetrabutylammonium fluoride (0.49 mL, 0.49 mmol, 1 M in tetrahydrofuran) was slowly added and the reaction was allowed to gradually warm to room temperature and stir for 3 days. The reaction was concentrated and the residue was taken up in dichloromethane. The solution was washed once with 1 N aqueous hydrochloric acid and once with brine. The organics were dried over magnesium sulfate, filtered, and concentrated. Purification by column chromatography (0-50% ethyl acetate/heptanes) gave the title compound (1.0 g, 75%) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 7.48 (d, J=7.61 Hz, 1H), 7.39 (d, J=1.76 Hz, 1H), 7.29 (dd, J=9.56, 1.95 Hz, 1H), 5.33-5.40 (m, 1H), 2.70 (d, J=5.46 Hz, 1H). to gradually warm to room temperature stir for 3 days The reaction was concentrated The solution was washed once with 1 N aqueous hydrochloric acid and once with brine The organics were dried over magnesium sulfate filtered concentrated Purification by column chromatography (0-50% ethyl acetate/heptanes)

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cs2CO3 (8.45 g, 26 mmol) was added to the solution of 1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanol (1.4 g, 5.2 mmol) in 10 ml of anhydrous 1,4-dioxane, the mixture was stirred for 5 minutes, then (S)-3-[4-(2-amino-6-chloro-pyrimidin-4-yl)-phenyl]-2-tert-butoxycarbonylamino-propionic acid (2.0 g, 5 mmol) was added, and the resulting mixture was heated at 110° C. overnight. After cooling, 5 ml of water was added and ethyl acetate (20 ml) was used to extract the product. The organic layer was dried over sodium sulfate. The solvent was removed by rotovap to give 2.6 g of (S)-3-(4-{2-amino-6-[1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethoxy]-pyrimidin-4-yl}phenyl)2tertbutoxycarbonylamino-propionic acid (yield: 82%). After cooling to extract the product The organic layer was dried over sodium sulfate The solvent was removed by rotovap

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

Procedure: TBAF (0.1 ml) was added to a solution of 4-bromo-2-fluoro-benzaldehyde (2.03 g, 10 mmol) and TMSCF3 (20 ml, 12 mmol) in 10 ml THF at 0° C. The formed mixture was warmed up to room temperature and stirred for 4 hours. The reaction mixture was then treated with 12 ml of 3M HCl and stirred overnight. The product was extracted with ethyl acetate (3×20 ml). The organic layer was separated and dried over sodium sulfate. The organic solvent was evaporated to give 2.4 g of 1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanol (yield: 90%). stirred overnight The product was extracted with ethyl acetate (3×20 ml) The organic layer was separated dried over sodium sulfate The organic solvent was evaporated