4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexanol

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 solution of 1,4-cyclohexanediol (5 g, 43 mmol), imidazole (2.92 g, 43 mmol) and NEt3 (7 mL) in CH2Cl2 (100 mL) cooled in an ice bath was added tert-butyldimethylsilyl chloride (6.47 g, 43 mmol). The mixture was stirred at room temperature overnight. Water was added and the organic phase was separated. The aqueous layer was extracted with EtOAc. The combined organic phase was dried over MgSO4 and concentrated. Chromatography on silica gel eluting with 3:1 EtOAc/hexanes provided the title compound (4.2 g, 42%) as an oil. MS calculated (M+H)+ 231, found 231. the organic phase was separated The aqueous layer was extracted with EtOAc The combined organic phase was dried over MgSO4 concentrated

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

Procedure: To a solution of 1,4-cyclohexanediol (5 g, 43 mmol), imidazole (2.92 g, 43 mmol) and NEt3 (7 mL) in CH2Cl2 (100 mL) cooled in an ice bath was added tert-butyldimethylsilyl chloride (6.47 g, 43 mmol). The mixture was stirred at room temperature overnight. Water was added and the organic phase was separated. The aqueous layer was extracted with EtOAc. The combined organic phase was dried over MgSO4 and concentrated. Chromatography on silica gel eluting with 3:1 EtOAc/hexanes provided the title compound (4.2 g, 42%) as an oil. MS calculated (M+H)+ 231, found 231. the organic phase was separated The aqueous layer was extracted with EtOAc The combined organic phase was dried over MgSO4 concentrated

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

Procedure: To a solution of 1,4-cyclohexanediol (5 g, 43 mmol), imidazole (2.92 g, 43 mmol) and NEt3 (7 mL) in CH2Cl2 (100 mL) cooled in an ice bath was added tert-butyldimethylsilyl chloride (6.47 g, 43 mmol). The mixture was stirred at room temperature overnight. Water was added and the organic phase was separated. The aqueous layer was extracted with EtOAc. The combined organic phase was dried over MgSO4 and concentrated. Chromatography on silica gel eluting with 3:1 EtOAc/hexanes provided the title compound (4.2 g, 42%) as an oil. MS calculated (M+H)+ 231. found 231. the organic phase was separated The aqueous layer was extracted with EtOAc The combined organic phase was dried over MgSO4 concentrated

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

Procedure: To a solution of 1,4-cyclohexanediol (5 g, 43 mmol), imidazole (2.92 g, 43 mmol) and NEt3 (7 mL) in CH2Cl2 (100 mL) cooled in an ice bath was added tert-butyldimethylsilyl chloride (6.47 g, 43 mmol). The mixture was stirred at room temperature overnight. Water was added and the organic phase was separated. The aqueous layer was extracted with EtOAc. The combined organic phase was dried over MgSO4 and concentrated. Chromatography on silica gel eluting with 3:1 EtOAc/hexanes provided the title compound (4.2 g, 42%) as an oil. MS calculated (M+H)+ 231. found 231. the organic phase was separated The aqueous layer was extracted with EtOAc The combined organic phase was dried over MgSO4 concentrated

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 solution of 1,4-cyclohexanediol (5 g, 43 mmol), imidazole (2.92 g, 43 mmol) and NEt3 (7 mL) in CH2Cl2 (100 mL) cooled in an ice bath was added tert-butyldimethylsilyl chloride (6.47 g, 43 mmol). The mixture was stirred at room temperature overnight. Water was added and the organic phase was separated. The aqueous layer was extracted with EtOAc. The combined organic phase was dried over MgSO4 and concentrated. Chromatography on silica gel eluting with 3:1 EtOAc/hexanes provided the title compound (4.2 g, 42%) as an oil. MS calculated (M+H)+231. Found 231. the organic phase was separated The aqueous layer was extracted with EtOAc The combined organic phase was dried over MgSO4 concentrated

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

Procedure: A solution of diisopropylazadicarboxylate (1.65 g, 8.16 mmol) in anhydrous tetrahydrofuran (5 mL) was added, dropwise, at 0° C., to a solution of 4-chloro-2-nitrophenol (0.75 g, 4.32 mmol), 4-(tert-butyl-dimethyl-silanyloxy)-cyclohexanol (1.2 g, 5.21 mmol) and triphenylphosphine (2.27 g, 8.65 mmol) in anhydrous tetrahydrofuran (10 mL). The resulting mixture was stirred at 0° C. for 1 hour and at room temperature overnight. The reaction mixture was then sonicated for 20 minutes at room temperature and for 30 minutes at 40° C. and then was stirred at room temperature for 24 hours. The solvent was evaporated under reduced pressure and the residue was partitioned between ethyl acetate and an aqueous solution of sodium bicarbonate (5%), the organic layer was separated and the aqueous layer was extracted 3 times with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The yellow oily residue was purified on a silica gel plug (hexane/EtOAc, from 99/1 to 90/10) to give a yellow oil. This material was dissolved in a mixture of ethyl acetate and hexane (1/1) and the resulting solution was washed twice with an aqueous solution of sodium hydroxide (3 M) and once with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to give 1.28 g (79% yield) of tert-butyl-[4-(4-chloro-2-nitro-phenoxy)-cyclohexyloxy]-dimethyl-silane as a light yellow oil. at 0° C. The reaction mixture was then sonicated for 20 minutes at room temperature and for 30 minutes at 40° C. was stirred at room temperature for 24 hours The solvent was evaporated under reduced pressure the residue was partitioned between ethyl acetate an aqueous solution of sodium bicarbonate (5%), the organic layer was separated the aqueous layer was extracted 3 times with ethyl acetate The combined organic extracts were washed with brine dried over anhydrous sodium sulfate filtered evaporated under reduced pressure The yellow oily residue was purified on a silica gel plug (hexane/EtOAc, from 99/1 to 90/10) to give a yellow oil the resulting solution was washed twice with an aqueous solution of sodium hydroxide (3 M) and once with brine dried over anhydrous sodium sulfate filtered evaporated under reduced pressure

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

Procedure: A solution of tert-butyldimethylsilyl chloride (1.5 g, 9.9 mmol) in anhydrous N,N-dimethylformamide (5 mL) was added, dropwise, at 0° C., to a solution of 1,4-cyclohexanediol (1.0 g, 8.6 mmol) and imidazole (1.5 g, 22.0 mmol) in anhydrous tetrahydrofuran (5 mL). After completion of the addition brine was added and the resulting mixture was extracted 3 times with ethyl acetate. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was purified on a silica gel plug (hexane/EtOAc, 80/20) to afford 1.3 g (66% yield) of 4-(tert-butyl-dimethyl-silanyloxy)-cyclohexanol as a colorless oil. at 0° C. was added the resulting mixture was extracted 3 times with ethyl acetate The combined organic extracts were washed with water and brine dried over anhydrous sodium sulfate filtered evaporated under reduced pressure The crude residue was purified on a silica gel plug (hexane/EtOAc, 80/20)

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

Procedure: To a solution of 6-butyl-3-(4-hydroxyphenyl)-2-methyl-5-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one (1.2 g), 4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexanol (1.2 g) and triphenylphosphine (1.4 g) in tetrahydrofuran (12 mL) was added dropwise diisopropyl azodicarboxylate (1.9 M toluene solution, 2.8 mL). After stirring for 2 hr, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and a mixture of the residue, hydroxylammonium chloride (0.87 g), sodium hydrogen carbonate (1.3 g) and dimethyl sulfoxide (9 mL) was stirred overnight at 90° C. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (9 mL). N,N′-carbonyldiimidazole (0.3 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.28 mL) were added, and the mixture was stirred at room temperature for 30 min. Tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 2.5 mL) was added, and the mixture was stirred overnight at 50° C. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound (0.37 g, 28%) as an amorphous solid. the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure a mixture of the residue, hydroxylammonium chloride (0.87 g), sodium hydrogen carbonate (1.3 g) and dimethyl sulfoxide (9 mL) was stirred overnight at 90° C The reaction mixture was diluted with ethyl acetate washed with water with saturated brine, and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was dissolved in tetrahydrofuran (9 mL) N,N′-carbonyldiimidazole (0.3 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.28 mL) were added the mixture was stirred at room temperature for 30 min Tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 2.5 mL) was added the mixture was stirred overnight at 50° C The reaction mixture was diluted with ethyl acetate washed with 5% aqueous potassium hydrogen sulfate solution with saturated brine, and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography