1-(4-bromophenyl)-2,2,2-trifluoroethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4′-bromo-2,2,2-trifluoroacetophenone (5.0 g, 19.76 mmol) in THF (50 mls) at 0° C. was added NaBH4 (1.5 g, 39.52 mmol). The mixture was warmed to room temperature and stirred for 1 hour. The reaction was complete by TLC (CH2Cl2). The mixture was quenched with H2O, rotary evaporated to remove most of the THF, and extracted 2 times with CH2C2. The organics were combined, washed with brine, concentrated to a small volume and filtered through a plug of silica gel. The silica was washed with CH2Cl2 to elute the product, and the resulting solution was concentrated to give 4.65 g of 1-(4-bromophenyl)-2,2,2-trifluoroethanol. Yield: 92%. The mixture was quenched with H2O rotary evaporated to remove most of the THF extracted 2 times with CH2C2 washed with brine concentrated to a small volume filtered through a plug of silica gel The silica was washed with CH2Cl2 to elute the product the resulting solution was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4′-bromo-2,2,2-trifluoroacetophenone (5.0 g, 19.76 mmol) in THF (50 mls) at 0° C. was added NaBH4 (1.5 g, 39.52 mmol). The mixture was warmed to room temperature and stirred for 1 hour. The reaction was complete by TLC (CH2Cl2). The mixture was quenched with H2O, rotary evaporated to remove most of the THF, and extracted 2 times with CH2Cl2. The organics were combined, washed with brine, concentrated to a small volume and filtered through a plug of silica gel. The silica was washed with CH2Cl2 to elute the product, and the resulting solution was concentrated to give 4.65 g of 1-(4-bromophenyl)-2,2,2-trifluoroethanol. Yield 92%. The mixture was quenched with H2O rotary evaporated to remove most of the THF extracted 2 times with CH2Cl2 washed with brine concentrated to a small volume filtered through a plug of silica gel The silica was washed with CH2Cl2 to elute the product the resulting solution was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 4′-bromo-2,2,2-trifluoroacetophenone (0.392 g, 2.00 mmol) and CH3NO2 (0.488 g, 8.0 mmol) in dry toluene (70 mL) containing N,N-diethylenediamine (30 mmol) is heated at reflux with a Dean and Stark trap until complete removal of H2O. The cooled solution is washed with 5% aqueous HCl, dried over MgSO4, filtered, evaporated in vacuo and the resulting residue when purified by chromatography gives the title compound. is heated The cooled solution is washed with 5% aqueous HCl dried over MgSO4 filtered evaporated in vacuo the resulting residue when purified by chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4′-bromo-2,2,2-trifluoroacetophenone (5.0 g, 19.76 mmol) in THF (50 mls) at 0° C. was added NaBH4 (1.5 g, 39.52 mmol). The mixture was warmed to room temperature and stirred for 1 hour. The reaction was complete by TLC (CH2Cl2). The mixture was quenched with H2O, rotary evaporated to remove most of the THF, and extracted 2 times with CH2Cl2. The organics were combined, washed with brine, concentrated to a small volume and filtered through a plug of silica gel. The silica was washed with CH2Cl2 to elute the product, and the resulting solution was concentrated to give 4.65 g of 1-(4-bromophenyl)-2,2,2-trifluoroethanol. Yield: 92%. The mixture was quenched with H2O rotary evaporated to remove most of the THF extracted 2 times with CH2Cl2 washed with brine concentrated to a small volume filtered through a plug of silica gel The silica was washed with CH2Cl2 to elute the product the resulting solution was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4′-bromo-2,2,2-trifluoroacetophenone (5.0 g, 19.76 mmol) in THF (50 mls) at 0° C. was added NaBH4 (1.5 g, 39.52 mmol). The mixture was warmed to room temperature and stirred for 1 hour. The reaction was complete by TLC (CH2Cl2). The mixture was quenched with H2O, rotary evaporated to remove most of the THF, and extracted 2 times with CH2Cl2. The organics were combined, washed with brine, concentrated to a small volume and filtered through a plug of silica gel. The silica was washed with CH2Cl2 to elute the product, and the resulting solution was concentrated to give 4.65 g of 1-(4-bromophenyl)-2,2,2-trifluoroethanol. Yield: 92%. The mixture was quenched with H2O rotary evaporated to remove most of the THF extracted 2 times with CH2Cl2 washed with brine concentrated to a small volume filtered through a plug of silica gel The silica was washed with CH2Cl2 to elute the product the resulting solution was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4′-bromo-2,2,2-trifluoroacetophenone (5.0 g, 19.76 mmol) in THF (50 mls) at 0° C. was added NaBH4 (1.5 g, 39.52 mmol). The mixture was warmed to room temperature and stirred for 1 hour. The reaction was complete by TLC (CH2Cl2). The mixture was quenched with H2O, rotary evaporated to remove most of the THF, and extracted 2 times with CH2Cl2. The organics were combined, washed with brine, concentrated to a small volume and filtered through a plug of silica gel. The silica was washed with CH2Cl2 to elute the product, and the resulting solution was concentrated to give 4.65 g of 1-(4-bromophenyl)-2,2,2-trifluoroethanol. Yield 92%. The mixture was quenched with H2O rotary evaporated to remove most of the THF extracted 2 times with CH2Cl2 washed with brine concentrated to a small volume filtered through a plug of silica gel The silica was washed with CH2Cl2 to elute the product the resulting solution was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4′-bromo-2,2,2-trifluoroacetophenone (5.0 g, 19.76 mmol) in THF (50 mls) at 0° C. was added NaBH4 (1.5 g, 39.52 mmol). The mixture was warmed to room temperature and stirred for 1 hour. The reaction was complete by TLC (CH2Cl2). The mixture was quenched with H2O, rotary evaporated to remove most of the THF, and extracted 2 times with CH2Cl2. The organics were combined, washed with brine, concentrated to a small volume and filtered through a plug of silica gel. The silica was washed with CH2Cl2 to elute the product, and the resulting solution was concentrated to give 4.65 g of 1-(4-bromophenyl)-2,2,2-trifluoroethanol. Yield 92%. The mixture was quenched with H2O rotary evaporated to remove most of the THF extracted 2 times with CH2Cl2 washed with brine concentrated to a small volume filtered through a plug of silica gel The silica was washed with CH2Cl2 to elute the product the resulting solution was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 4′-bromo-2,2,2-trifluoroacetophenone (0.392 g, 2.00 mmol). and CH3NO2 (0.488 g, 8.0 mmol) in dry toluene (70 mL) containing N,N-diethylenediamine (30 mmol) is heated at reflux with a Dean and Stark trap until complete removal of H2O. The cooled solution is washed with 5% aqueous HCl, dried over MgSO4, filtered, evaporated in vacuo and the resulting residue when purified by chromatography gives the title compound. is heated The cooled solution is washed with 5% aqueous HCl dried over MgSO4 filtered evaporated in vacuo the resulting residue when purified by chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4′-Bromo-2,2,2-trifluoracetophenone (1.80 mL, 11.9 mmol) was dissolved in tetrahydrofuran (60 mL), cooled to 0° C., and methylmagnesium bromide (19.8 mL, 59.3 mmol) was added. The reaction mixture was maintained at 0° C. for 1 hour and then allowed to warm to ambient temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, concentrated in vacuo and the crude residue was purified directly by MPLC on silica gel (using a gradient elution of 0-25% ethyl acetate in hexanes to afford a racemic mixture of the title compound. The mixture was resolved to the constituent enantiomers by Chiral SFC purification (Chiral Technology AZ-H 2.1×25 cm, 5 uM column; mobile phase: 5% methanol/CO2) to afford the title compounds as single enantiomers. Intermediate #11-1: First enantiomer to elute; (S or R)-2-(4-Bromophenyl)-1,1,1-trifluoropropan-2-ol; 1H NMR (500 MHz, CDCl3) δ 7.53-7.52 (d, 2H), 7.46-7.45 (d, 2H), 2.64 (bs, 1H), 1.76 (s, 3H). Intermediate #11-2: Second enantiomer to elute; (S or R)-2-(4-Bromophenyl)-1,1,1-trifluoropropan-2-ol; 1H NMR (500 MHz, CDCl3) δ 7.53-7.52 (d, 2H), 7.46-7.45 (d, 2H), 2.64 (bs, 1H), 1.76 (s, 3H). The reaction mixture was maintained at 0° C. for 1 hour to warm to ambient temperature overnight The reaction was quenched with saturated aqueous ammonium chloride extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous MgSO4 filtered concentrated in vacuo the crude residue was purified directly by MPLC on silica gel ( a gradient elution of 0-25% ethyl acetate in hexanes to afford