2-(4-tert-Butylphenyl)ethanol

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

Conditions: temp:70.01; pressure:0.00; stir:

Procedure: Dilution of the aliquot (2 uL) with DMSO (200 uL).

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

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

Procedure: 5.4 g (0.03 mol) of 2-(4-tert-butylphenyl)ethanol were added dropwise at 50° C. to a suspension of 1.2 g (0.03 mol) of sodium hydride (60% dispersion in oil) in 50 ml of dry dimethylformamide, and the mixture was stirred until the evolution of hydrogen had ceased. The mixture was cooled to 0° C., and 4.7 g (0.025 mol) of 4-chloro-5-methoxy-6-methoxymethylpyrimidine (Coll. Czechoslov. Chem. Commun. 33, 2266 (1968)) were added. The mixture was stirred for 1 hour at room temperature and for 2 hours at 100° C. After the solvent had been stripped off, the residue was taken up in dichloromethane/water, and the organic phase was dried and evaporated on a rotary evaporator. The crude product was chromatographed on silica gel using ethyl acetate. 3.8 g (46% of theory) of 4-[2-(4-tert-butylphenyl)ethoxy]-5 -methoxy-6 -methoxymethylpyrimidine were obtained in the form of a yellow oil. the organic phase was dried evaporated on a rotary evaporator The crude product was chromatographed on silica gel

Conditions: temp:-17.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2 g of 4-hydroxypteridine in 20 mL of CH2Cl2 under nitrogen was added 1.2 g of 25 pyridine. The mixture was cooled to -30° C and over a 15 minute period a solution of 4.82 g of triphenyl phosphite in CH2Cl2 was added simultaneously with addition of chlorine gas. The mixture was stirred for one and one half hours while maintaining the temperature at -15 to -20° C. The mixture was then allowed to warm to 10° C., and a solution of 2.67 g of 2-[4-(t-butyl)phenyl]ethanol in CH2Cl2 was added. The resulting mixture was refluxed for 45 minutes, then cooled and diluted into toluene. The toluene solution was washed with dilute base, then filtered through phase separating paper and concentrated in vacuo. The resulting bluish oil was adsorbed onto silica gel and chromatographed (silica gel, CH2Cl2 →80% CH2Cl2, 20% EtOAc). Fractions containing the major product were combined. The product was then recrystallized from petroleum ether/CH2Cl2. Yield 60 mg. M.P. 149° C. to warm to 10° C. The resulting mixture was refluxed for 45 minutes cooled The toluene solution was washed with dilute base filtered through phase separating paper concentrated in vacuo chromatographed (silica gel, CH2Cl2 →80% CH2Cl2, 20% EtOAc) Fractions containing the major product The product was then recrystallized from petroleum ether/CH2Cl2

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

Procedure: A mixture consisting of 1.86 g (0.011 mole) of 4-chloropyrido-[2,3-d]pyrimidine, 2.0 g (0.011 mole) of 2-[4-(t-butyl)phenyl]ethanol, and 40 mL of toluene containing a little HCl gas was stirred at room temperature. The mixture was then cooled, and a yellow solid was collected. This was washed with hexane, then partitioned between 1N NaOH and CH2Cl2. The CH2Cl2 layer was dried over MgSO4, then the solvent was removed under vacuum to leave a yellow solid, which was recrystallized from hexane. Yield 2.5 g. M.P. 77-79° C. The mixture was then cooled a yellow solid was collected This was washed with hexane partitioned between 1N NaOH and CH2Cl2 The CH2Cl2 layer was dried over MgSO4 the solvent was removed under vacuum to leave a yellow solid, which was recrystallized from hexane

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

Procedure: A solution of 2-(4-tert-butylphenyl)ethanol (5.35 g, 30.0 mmol) in chloroform (150 mL) was cooled in ice and Dess-Martin periodinane (16.5 g, 39.0 mmol) was added thereto. The mixture was warmed to room temperature and stirred for 3 hr. The reaction mixture was diluted with chloroform (150 mL), followed by cooling in ice. Thereafter, saturated aqueous sodium thiosulfate solution was added thereto and the mixture was stirred for 5 min. The mixture was extracted three times with chloroform and then the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The desiccant was filtered off and then the filtrate was concentrated under reduced pressure. The resulting precipitate was filtered again, followed by washing with chloroform. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to afford the title compound as a yellow oil (4.24 g). by cooling in ice the mixture was stirred for 5 min The mixture was extracted three times with chloroform the organic layer was washed with brine dried over anhydrous magnesium sulfate The desiccant was filtered off the filtrate was concentrated under reduced pressure The resulting precipitate was filtered again by washing with chloroform The filtrate was concentrated under reduced pressure the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1)

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

Procedure: A solution of 2-(4-tert-butylphenyl)ethanol (5.35 g, 30.0 mmol) in chloroform (150 mL) was cooled in ice and Dess-Martin periodinane (16.5 g, 39.0 mmol) was added thereto. The mixture was warmed to room temperature and stirred for 3 hr. The reaction mixture was diluted with chloroform (150 mL), followed by cooling in ice. Thereafter, saturated aqueous sodium thiosulfate solution was added thereto and the mixture was stirred for 5 min. The mixture was extracted three times with chloroform and then the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The desiccant was filtered off and then the filtrate was concentrated under reduced pressure. The resulting precipitate was filtered again, followed by washing with chloroform. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to afford the title compound as a yellow oil (4.24 g). by cooling in ice the mixture was stirred for 5 min The mixture was extracted three times with chloroform the organic layer was washed with brine dried over anhydrous magnesium sulfate The desiccant was filtered off the filtrate was concentrated under reduced pressure The resulting precipitate was filtered again by washing with chloroform The filtrate was concentrated under reduced pressure the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1)

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

Procedure: 5.4 g (0.03 mol) of 2-(4-tert-butylphenyl)ethanol were added dropwise at 50° C. to a suspension of 1.2 g (0.03 mol) of sodium hydride (60% dispersion in oil) in 50 ml of dry dimethylformamide, and the mixture was stirred until the evolution of hydrogen had ceased. The mixture was cooled to 0° C., and 4.7 g (0.025 mol) of 4-chloro-5-methoxy-6-methoxymethylpyrimidine (Coll. Czechoslov. Chem. Commun. 33, 2266 (1968)) were added. The mixture was stirred for 1 hour at room temperature and for 2 hours at 100° C. After the solvent had been stripped off, the residue was taken up in dichloromethane/water, and the organic phase was dried and evaporated on a rotary evaporator. The crude product was chromatographed on silica gel using ethyl acetate. 3.8 g (46% of theory) of 4-[2-(4-tert-butylphenyl)ethoxy]-5 -methoxy-6 -methoxymethylpyrimidine were obtained in the form of a yellow oil. the organic phase was dried evaporated on a rotary evaporator The crude product was chromatographed on silica gel

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

Procedure: To a solution of 1.1 g of sodium hydride in 50 ml of DMF, 4.0 g of 2-[4-(t-butyl)phenyl]ethanol was added, and the mixture was stirred at room temperature for one hour. Then 3.6 g of 4-chloroquinazoline in 20 ml of DMF were added, and the mixture was stirred at room temperature overnight. The mixture was then poured into a mixture of ice in water. The product was extracted into CH2Cl2, and the resulting solution was concentrated to dryness. TLC showed one major spot and five minor spots. The product was purified by HPLC (silica gel, CH2Cl2). The fractions containing the major product were collected and concentrated, giving 1.9 g of the title product. Yield: 28.4%. M.P. 70°-71° C. the mixture was stirred at room temperature overnight The product was extracted into CH2Cl2 the resulting solution was concentrated to dryness The product was purified by HPLC (silica gel, CH2Cl2) The fractions containing the major product were collected concentrated

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 1.1 g of sodium hydride in 50 ml of DMF, 4.0 g of 2-[4-(t-butyl)phenyl]ethanol was added, and the mixture was stirred at room temperature for one hour. Then 3.6 g of 4-chloroquinazoline in 20 ml of DMF were added, and the mixture was stirred at room temperature overnight. The mixture was then poured into a mixture of ice in water. The product was extracted into CH2Cl2, and the resulting solution was concentrated to dryness. TLC showed one major spot and five minor spots. The product was purified by HPLC (silica gel, CH2Cl2). The fractions containing the major product were collected and concentrated, giving 1.9 g of the title product. Yield: 28.4%. M.P. 70°-71° C. the mixture was stirred at room temperature overnight The product was extracted into CH2Cl2 the resulting solution was concentrated to dryness The product was purified by HPLC (silica gel, CH2Cl2) The fractions containing the major product were collected concentrated