2-(trifluoromethoxy)benzenethiol

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 min. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (magnesium sulphate), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (magnesium sulphate) concentrated in vacuo

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 min. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (magnesium sulphate), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (magnesium sulphate) concentrated in vacuo

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 min. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (magnesium sulphate), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (magnesium sulphate) concentrated in vacuo

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 min. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (magnesium sulphate), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (magnesium sulphate) concentrated in vacuo

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

Procedure: The compound was prepared following an analogous procedure to the one described for the synthesis 2-{2-[3-[3-(2-methoxy-phenylsulfanyl)-propyl]-3-(trans-4-methyl -cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-2-methyl-propionic acid using 2-trifluoromethoxy -thiophenol and 2-(2-amino-thiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester. The compound was prepared

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 minutes. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were extracted with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (MgSO4), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were extracted with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (MgSO4) concentrated in vacuo

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

Procedure: The compound was prepared following an analogous procedure to the one described for the synthesis 2-{2-[3-[3-(2-methoxy-phenylsulfanyl)-propyl]-3-(trans-4-methyl-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-2-methyl-propionic acid using 2-trifluoromethoxy-thiophenol and 2-(2-amino-thiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester. The compound was prepared

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(trifluoromethoxy)benzenethiol (1.035 g, 5.33 mmol) in DMF (15 mL) at 0° C. was added K2CO3 (921 mg, 6.66 mmol). The solution was warmed to ambient temperature over 10 min before 4-fluorobenzonitrile (613 mg, 5.06 mmol) was added at once. The mixture was heated to 120° C. for 16 hours, then was then cooled and poured onto ice. The mixture was diluted with EtOAc, the layers separated, and the organics were washed successively with sat. NaHCO3 and brine (2×). The organics were dried (MgSO4), filtered, and purified by Biotage SP1 (DCM/hexanes gradient) to afford 4-((2-(trifluoromethoxy)phenyl)thio)benzonitrile (1.098 g, 74%) as a golden oil. was added at once was then cooled poured onto ice the layers separated the organics were washed successively with sat. NaHCO3 and brine (2×) The organics were dried (MgSO4) filtered purified by Biotage SP1 (DCM/hexanes gradient)

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

Procedure: The reaction of the mesylate from experiment A2 with 2-trifluoromethoxy-benzenethiol yielded (2S,4R)-2-(1-cyano-cyclopropylcarbamoyl)-4-(2-trifluoromethoxy-phenylsulfanyl)-pyrrolidine-1-carboxylic acid t-butyl ester as a colorless foam. MS: 470.3 [M−H]−.

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 minutes. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were extracted with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (MgSO4), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were extracted with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (MgSO4) concentrated in vacuo

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 min. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (magnesium sulphate), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (magnesium sulphate) concentrated in vacuo

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

Procedure: To a solution of methyl iodide (59.0 g, 0.41 mol) in DMF (150 mL) was added potassium carbonate (23.0 g, 0.16 mol). 2-(Trifluoromethoxy)thiophenol (16.0 g, 0.08 mol) was added in portions during 30 min. The reaction mixture was then stirred vigorously overnight. Water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (2×150 mL). The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL), dried (magnesium sulphate), and concentrated in vacuo to give 15.0 g of 1-methylsulfanyl-2-trifluoromethoxybenzene. The reaction mixture was extracted with ethyl acetate (2×150 mL) The combined organic phases were washed with a 50% saturated aqueous solution of sodium chloride (4×100 mL) dried (magnesium sulphate) concentrated in vacuo