TRIETHYL(TRIFLUOROMETHYL)SILANE

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 25 g (0.17 mol) of chlorotriethylsilane and 40 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 40 mL (0.43 mol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 66mL (0.24 mol) of hexaethylphosphorous triamide, allowed to stir at -78° C. for two hours, and allowed to stir at room temperature overnight. Low boiling components were then short path distilled into a cold (-78° C.) receiving flask at >1 torr with the pot temperature kept at <50° C. The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation to give 22.0 g of 98% pure (69% yield) triethyltrifluoromethylsilane: bp 52°-54° C. at 10 torr; 1H NMR (CDCl3) δ 0.59-1.16 (m); 19F NMR (CDCl3, relative to CFCl3) - 61.3 ppm (s); IR (neat) 2960, 2915, 2882, 1458, 1413, 1206, 1055, 1020, 734, 693 cm-1 ; mass spectrum (70 eV) m/z (relative intensity) 115 (66, M-CF3), 105 (46), 87 (85), 77 (100), 59 (56), 49 (41), 47 (37), 41 (38). Anal. Calcd. for C7H15F3Si: C, 45.62; H, 8.20. Found: C, 47.53; H, 8.56. A flask equipped with a dry ice condenser was flame dried under a nitrogen stream condensed into a graduated tube was warmed to room temperature to distill into the flask to stir at room temperature overnight short path distilled into a cold (-78° C.) kept at <50° C The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation

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

Procedure: A mixture of 74 mg (1.3 mmol) of ground ammonium bifluoride, 174 mg (1.1 mmol) of 1,4-naphthoquinone, and 1 mL of N,N-dimethylformam:ide was treated with 239 mg (1.3 mmol) of triethyltrifluoromethylsilane and stirred vigorously at room temperature for one hour. Gas chromatographic analysis of the reaction mixture showed that the major naphthalene-desired product was 1,4-dihydro-4-hydroxy-1-oxo-4-trifluoromethylnaphthalene.

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

Procedure: A mixture of 74 mg (1.3 mmol) of ground ammonium bifluoride (NH4HF2), 119 mg (1.1 mmol) of 1,4-benzoquinone, and 2 mL of acetonitrile was treated with 239 mg (1.3 mmol) of triethyltrifluoromethylsilane and stirred vigorously at room temperature for 4 hours. The mixture was filtered and the filter cake was washed with dichloromethane. Concentration of the combined filtrates gave a black solid which was triturated with dichloromethane. The resulting mixture was filtered and the filter cake was washed with dichloromethane. Concentration of the combined filtrates afforded a brown solid which was purified by PTLC (one 2 mm silica gel plate eluted with a 2% methanol-98% dichloromethane) to give 83 mg (42% yield) of 4-hydroxy-4-tri -fluoromethyl-2,5-cyclohexadien-1-one. The mixture was filtered the filter cake was washed with dichloromethane Concentration of the combined filtrates gave a black solid which was triturated with dichloromethane The resulting mixture was filtered the filter cake was washed with dichloromethane Concentration of the combined filtrates afforded a brown solid which was purified by PTLC (one 2 mm silica gel plate eluted with a 2% methanol-98% dichloromethane)

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

Procedure: A mixture of 74 mg (1.3 mmol) of ground ammonium bifluoride (NH4HF2), 119 mg (1.1 mmol) of 1,4-benzoquinone, and 2 mL of acetonitrile was treated with 239 mg (1.3 mmol) of triethyltrifluoromethylsilane and stirred vigorously at room temperature for 4 hours. The mixture was filtered and the filter cake was washed with dichloromethane. Concentration of the combined filtrates gave a black solid which was triturated with dichloromethane. The resulting mixture was filtered and the filter cake was washed with dichloromethane. Concentration of the combined filtrates afforded a brown solid which was purified by PTLC (one 2 mm silica gel plate eluted with a 2% methanol-98% dichloromethane) to give 83 mg (42% yield) of 4-hydroxy-4-tri -fluoromethyl-2,5-cyclohexadien-1-one. The mixture was filtered the filter cake was washed with dichloromethane Concentration of the combined filtrates gave a black solid which was triturated with dichloromethane The resulting mixture was filtered the filter cake was washed with dichloromethane Concentration of the combined filtrates afforded a brown solid which was purified by PTLC (one 2 mm silica gel plate eluted with a 2% methanol-98% dichloromethane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 25g (0.17 mol) of chlorotriethylsilane and 40 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 40 mL (0.43 mol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 66mL (0.24 mol) of hexaethylphosphorous triamide, allowed to stir at -78° C. for two hours, and allowed to stir at room temperature overnight. Low boiling components were then short path distilled into a cold (-78° C.) receiving flask at>1 torr with the pot temperature kept at<50° C. The distillate was further fractionated by removal of the dichloromethane (40-45° C. at atmospheric pressure) and short path distillation to give 22.0 g of 98% pure (69% yield) triethyltrifluoromethylsilane: bp 52-54° C. at 10 torr; 1H NMR (CDCl3) δ 0.59-1.16 (m); 19F NMR (CDCl3, relative to CFCl3) -61.3 ppm (s); IR (neat) 2960, 2915, 2882, 1458, 1413, 1206, 1055, 1020, 734, 693 cm-1; mass spectrum (70 eV) m/z (relative intensity) 115 (66, M-CF3), 105 (46), 87 (85), 77 (100), 59 (56), 49 (41), 47 (37), 41 (38). Anal. Calcd. for C7H15F3Si: C, 45.62; H, 8.20. Found: C, 47.53; H, 8.56. A flask equipped with a dry ice condenser was flame dried under a nitrogen stream condensed into a graduated tube was warmed to room temperature to distill into the flask to stir at room temperature overnight short path distilled into a cold (-78° C.) kept at<50° C The distillate was further fractionated by removal of the dichloromethane (40-45° C. at atmospheric pressure) and short path distillation

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sealed tube charged with 1-(2-(4-(3-iodothiophen-2-yl)pyrimidin-2-ylamino)ethyl)-5,5-dimethylimidazolidine-2,4-dione (0.300 g, 0.656 mmol), copper (I) iodide (0.275 g, 1.44 mmol), spray-dried potassium fluoride (0.075 g, 1.3 mmol), triethyl(trifluoromethyl)silane (0.25 mL, 1.3 mmol), DMF (1.0 mL), and NMP (1.0 mL) was heated to 80° C. and allowed to stir for 72 h. At that time, the mixture was diluted with 20 mL dichloromethane and filtered. The pale green filtrate was then purified through Celite and the plug was washed with 10% MeOH/dichloromethane and H2O. The organic solvents were removed from the biphasic mixture in vacuo and the aqueous residue was then partitioned between dichloromethane and H2O. The organic phase was separated, concentrated and the residue purified by flash chromatography, eluting with 1-6% MeOH/dichloromethane to afford the product as a white solid. MS (M+H)+ 400. filtered The pale green filtrate was then purified through Celite the plug was washed with 10% MeOH/dichloromethane and H2O The organic solvents were removed from the biphasic mixture in vacuo the aqueous residue was then partitioned between dichloromethane and H2O The organic phase was separated concentrated the residue purified by flash chromatography eluting with 1-6% MeOH/dichloromethane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sealed tube charged with 1-(2-(4-(3-iodothiophen-2-yl)pyrimidin-2-ylamino)ethyl)-5,5-dimethylimidazolidine-2,4-dione (0.300 g, 0.656 mmol), copper (I) iodide (0.275 g, 1.44 mmol), spray-dried potassium fluoride (0.075 g, 1.3 mmol), triethyl(trifluoromethyl)silane (0.25 mL, 1.3 mmol), DMF (1.0 mL), and NMP (1.0 mL) was heated to 80° C. and allowed to stir for 72 h. At that time, the mixture was diluted with 20 mL dichloromethane and filtered. The pale green filtrate was then purified through Celite and the plug was washed with 10% MeOH/dichloromethane and H2O. The organic solvents were removed from the biphasic mixture in vacuo and the aqueous residue was then partitioned between dichloromethane and H2O. The organic phase was separated, concentrated and the residue purified by flash chromatography, eluting with 1-6% MeOH/dichloromethane to afford the product as a white solid. MS (M+H)+ 400. filtered The pale green filtrate was then purified through Celite the plug was washed with 10% MeOH/dichloromethane and H2O The organic solvents were removed from the biphasic mixture in vacuo the aqueous residue was then partitioned between dichloromethane and H2O The organic phase was separated concentrated the residue purified by flash chromatography eluting with 1-6% MeOH/dichloromethane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 25 g (0.17 mol) of chlorotriethylsilane and 40 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 40 mL (0.43 mol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 66mL (0.24 mol) of hexaethylphosphorous triamide, allowed to stir at -78° C. for two hours, and allowed to stir at room temperature overnight. Low boiling components were then short path distilled into a cold (-78° C.) receiving flask at >1 torr with the pot temperature kept at <50° C. The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation to give 22.0 g of 98% pure (69% yield) triethyltrifluoromethylsilane: bp 52°-54° C. at 10 torr; 1H NMR (CDCl3) δ 0.59-1.16 (m); 19F NMR (CDCl3, relative to CFCl3) - 61.3 ppm (s); IR (neat) 2960, 2915, 2882, 1458, 1413, 1206, 1055, 1020, 734, 693 cm-1 ; mass spectrum (70 eV) m/z (relative intensity) 115 (66, M-CF3), 105 (46), 87 (85), 77 (100), 59 (56), 49 (41), 47 (37), 41 (38). Anal. Calcd. for C7H15F3Si: C, 45.62; H, 8.20. Found: C, 47.53; H, 8.56. A flask equipped with a dry ice condenser was flame dried under a nitrogen stream condensed into a graduated tube was warmed to room temperature to distill into the flask to stir at room temperature overnight short path distilled into a cold (-78° C.) kept at <50° C The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-(4-iodo-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (470 mg, 1.35 mmol), copper (I) iodide (256 mg, 1.35 mmol) and potassium fluoride (78 mg, 1.35 mmol) in anhydrous DMF/HMPA (2 ml/2 mL) was added triethyl(trifluoromethyl)silane (745 mg, 4.04 mmol). The mixture was heated to 70° C. under N2 in a sealed tube. After 10 h, the reaction was quenched with NH4Cl (sat'd) (2 mL), extracted with ether (5 mL×5) and washed with distilled water (5 mL×5). The combined organic phase was dried over Mg2SO4 and purified on silica (EtOAc/Hex, 10-30%) to afford the title compound (0.29 g, 74%) as a yellow syrup: LC-MS (ES) m/z 291 (M+H)+. the reaction was quenched with NH4Cl (sat'd) (2 mL) extracted with ether (5 mL×5) washed with distilled water (5 mL×5) The combined organic phase was dried over Mg2SO4 purified on silica (EtOAc/Hex, 10-30%)

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

Procedure: A mixture of 74 mg (1.3 mmol) of ground ammonium bifluoride, 174 mg (1.1 mmol) of 1,4-naphthoquinone, and 1 mL of N,N-dimethylformamide was treated with 239 mg (1.3 mmol) of triethyltrifluoromethylsilane and stirred vigorously at room temperature for one hour. Gas chromatographic analysis of the reaction mixture showed that the major naphthalene-desired product was 1,4-dihydro-4-hydroxy-1-oxo-4-trifluoromethylnaphthalene.