2-(Trifluoromethoxy)benzyl alcohol

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

Procedure: To a stirred solution of 2-trifluoromethoxybenzyl alcohol (0.81 g, 4.5 mmol) from Step 1 above in ether (20 mL) at 0° C. was added triphenylphosphine (2.4 g, 9.2 mmol) and CBr4 (3.0 g, 9.2 mmol). The mixture was warmed to ambient temperature and stirred for 18 h. The ether was decanted from the gummy precipitate of triphenylphosphine oxide and evaporated under reduced pressure. The residue was purified by pressurized silica gel column chromatography using hexanes as eluant to give 2-trifluoromethoxybenzyl bromide as a colorless liquid (TLC Rf =0.80 (hexanes)). The ether was decanted from the gummy precipitate of triphenylphosphine oxide evaporated under reduced pressure The residue was purified by pressurized silica gel column chromatography

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

Procedure: To a stirred solution of 2-trifluoromethoxybenzoic acid (1.0 g, 5.2 mmol) in THF (25 mL) at 0° C. was added borane-THF complex (15 mL of a 1.0 M solution in THF, 15 mmol). The solution was warmed to ambient temperature and stirred for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (75 mL) and saturated aqueous NaHCO3 (75 mL). The organic phase was dried (MgSO4), filtered and the solvent was removed under reduced pressure to give 2-trifluoromethoxybenzyl alcohol as a colorless liquid (TLC Rf =0.2 (1:3 EtOAc-hexanes)). The solvent was removed under reduced pressure the residue was partitioned between EtOAc (75 mL) and saturated aqueous NaHCO3 (75 mL) The organic phase was dried (MgSO4) filtered the solvent was removed under reduced pressure

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

Procedure: This compound was prepared according to the procedure of example 69, substituting 3-(3-benzyl-8-trifluoromethyl-quinolin-4-yl)-phenol and (2-trifluoromethoxy-phenyl)-methanol. MS (ESI) m/z 554. This compound was prepared

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

Procedure: To a stirred solution of 2-trifluoromethoxybenzyl alcohol (0.81 g, 4.5 mmol) from Step 1 above in ether (20 mL) at 0° C. was added triphenylphosphine (2.4 g, 9.2 mmol) and CBr4 (3.0 g, 9.2 mmol). The mixture was warmed to ambient temperature and stirred for 18 h. The ether was decanted from the gummy precipitate of triphenylphosphine oxide and evaporated under reduced pressure. The residue was purified by pressurized silica gel column chromatography using hexanes as eluant to give 2-trifluoromethoxybenzyl bromide as a colorless liquid (TLC Rf =0.80 (hexanes)). The ether was decanted from the gummy precipitate of triphenylphosphine oxide evaporated under reduced pressure The residue was purified by pressurized silica gel column chromatography

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

Procedure: To a stirred solution of 2-trifluoromethoxybenzoic acid (1.0 g, 5.2 mmol) in THF (25 mL) at 0° C. was added borane-THF complex (15 mL of a 1.0 M solution in THF, 15 mmol). The solution was warmed to ambient temperature and stirred for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (75 mL) and saturated aqueous NaHCO3 (75 mL). The organic phase was dried (MgSO4), filtered and the solvent was removed under reduced pressure to give 2-trifluoromethoxybenzyl alcohol as a colorless liquid (TLC Rf =0.2 (1:3 EtOAc-hexanes)). The solvent was removed under reduced pressure the residue was partitioned between EtOAc (75 mL) and saturated aqueous NaHCO3 (75 mL) The organic phase was dried (MgSO4) filtered the solvent was removed under reduced pressure

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

Procedure: 5 g (26 mmol) of 2-trifluoromethoxybenzyl alcohol and 8.5 g (24.7 mmol) of triphenylphosphonium bromide are heated under reflux in 100 ml of acetonitrile for 3 h. After cooling, the resulting precipitate is filtered off with suction and dried. 13.5 g (quant.) of the title compound are obtained. After cooling the resulting precipitate is filtered off with suction dried

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Trifluoromethoxy)benzyl alcohol (200 mg, 1.04 mmol), thiourea (100 mg, 1.31 mmol), aqueous hydrochloric acid (2M) (1.6 ml) and 1,4-dioxane (3 ml) were mixed and the mixture heated in a sealed vessel in the microwave at 140° C. for 10 minutes. Potassium carbonate (620 mg, 4.5 mmol) and 3-methanesulfonyl-5,5-dimethyl-4,5-dihydroisoxazole (220 mg, 1.24 mmol) were added and the mixture was stirred in an open vessel for 10 minutes. The mixture was heated in a sealed vessel in the microwave at 150° C. for 10 minutes. The mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, dried over magnesium sulfate and concentrated. The crude material was purified by chromatography on silica gel (eluent: ethyl acetate/hexane) to give the product as a white solid (50 mg, 15% yield). 1H-NMR (400 MHz, CDCl3): 1.41 (6H, s, Me), 2.78 (2H, s, CH2), 4.32 (2H, s, CH2), 7.2-7.4 (2H, m, CH), 7.57 (1H, m, CH). The mixture was heated in a sealed vessel in the microwave at 150° C. for 10 minutes extracted with ethyl acetate The organic extract was washed with water dried over magnesium sulfate concentrated The crude material was purified by chromatography on silica gel (eluent: ethyl acetate/hexane)