65678-11-7

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(1,1-dimethylethyl)-4-hydroxybenzaldehyde (Intermediate 108, 550 mg) and hydroxylamine hydrochloride (322 mg, 4.63 mmol) were stirred in 8.0 mL of acetic acid at reflux for 1 h. After cooling down to 0° C., the mixture was poured into Et2O and washed once with water and once with NaOH (5% aqueous solution). The collected aqueous phases were extracted with Et2O (two times) and the combined organic phases were dried over Na2SO4, filtered, evaporated and triturated with pentane affording 540 mg of the title compound. at reflux for 1 h washed once with water and once with NaOH (5% aqueous solution) The collected aqueous phases were extracted with Et2O (two times) the combined organic phases were dried over Na2SO4 filtered evaporated triturated with pentane affording 540 mg of the title compound

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(1,1-dimethylethyl)-4-hydroxybenzaldehyde (Intermediate 108, 550 mg) and hydroxylamine hydrochloride (322 mg, 4.63 mmol) were stirred in 8.0 mL of acetic acid at reflux for 1 h. After cooling down to 0° C., the mixture was poured into Et2O and washed once with water and once with NaOH (5% aqueous solution). The collected aqueous phases were extracted with Et2O (two times) and the combined organic phases were dried over Na2SO4, filtered, evaporated and triturated with pentane affording 540 mg of the title compound. at reflux for 1 h washed once with water and once with NaOH (5% aqueous solution) The collected aqueous phases were extracted with Et2O (two times) the combined organic phases were dried over Na2SO4 filtered evaporated triturated with pentane affording 540 mg of the title compound

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(1,1-dimethylethyl)phenol (10 g, 66.67 mmol) was dissolved in 40 mL of MeOH and NaOH (40 g, 1 mol) dissolved in 40 mL of water was added dropwise. Then 40 mL of CHCl3 was added (during the course of 1 h) at 60° C. The reaction mixture was stirred at that temperature for 3 h. After cooling down to r.t., the mixture was cooled to 0° C. and 4M HCl was added until the solution reached pH 5-6. The mixture was extracted with DCM (three times) and the collected organic were dried over Na2SO4, filtered and evaporated. The crude was charged on a silica gel column and eluted with Cyclohexane/EtOAc (from 100:0 to 80:20 Cyclohexane/EtOAc, then plateau at 80:20) affording 766 mg of the of the title compound. was added dropwise the mixture was cooled to 0° C. The mixture was extracted with DCM (three times) the collected organic were dried over Na2SO4 filtered evaporated The crude was charged on a silica gel column eluted with Cyclohexane/EtOAc (from 100:0 to 80:20 Cyclohexane/EtOAc

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(1,1-dimethylethyl)-4-hydroxybenzaldehyde (Reference Intermediate R9, 550 mg) and hydroxylamine hydrochloride (322 mg, 4.63 mmol) were stirred in 8.0 mL of acetic acid at reflux for 1 h. After cooling down to 0° C., the mixture was poured into Et2O and washed once with water and once with NaOH (5% aqueous solution). The collected aqueous phases were extracted with Et2O (two times) and the combined organic phases were dried over Na2SO4, filtered, evaporated and triturated with pentane affording 540 mg of the title compound. at reflux for 1 h washed once with water and once with NaOH (5% aqueous solution) The collected aqueous phases were extracted with Et2O (two times) the combined organic phases were dried over Na2SO4 filtered evaporated triturated with pentane affording 540 mg of the title compound

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(1,1-dimethylethyl)-4-hydroxybenzaldehyde (Reference Intermediate R9, 550 mg) and hydroxylamine hydrochloride (322 mg, 4.63 mmol) were stirred in 8.0 mL of acetic acid at reflux for 1 h. After cooling down to 0° C., the mixture was poured into Et2O and washed once with water and once with NaOH (5% aqueous solution). The collected aqueous phases were extracted with Et2O (two times) and the combined organic phases were dried over Na2SO4, filtered, evaporated and triturated with pentane affording 540 mg of the title compound. at reflux for 1 h washed once with water and once with NaOH (5% aqueous solution) The collected aqueous phases were extracted with Et2O (two times) the combined organic phases were dried over Na2SO4 filtered evaporated triturated with pentane affording 540 mg of the title compound

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(1,1-dimethylethyl)phenol (10 g, 66.67 mmol) was dissolved in 40 mL of MeOH and NaOH (40 g, 1 mol) dissolved in 40 mL of water was added dropwise. Then 40 mL of CHCl3 was added (during the course of 1 h) at 60° C. The reaction mixture was stirred at that temperature for 3 h. After cooling down to r.t., the mixture was cooled to 0° C. and 4M HCl was added until the solution reached pH 5-6. The mixture was extracted with DCM (three times) and the collected organic were dried over Na2SO4, filtered and evaporated. The crude was charged on a silica gel column and eluted with Cyclohexane/EtOAc (from 100:0 to 80:20 Cyclohexane/EtOAc, then plateau at 80:20) affording 766 mg of the of the title compound. was added dropwise the mixture was cooled to 0° C. The mixture was extracted with DCM (three times) the collected organic were dried over Na2SO4 filtered evaporated The crude was charged on a silica gel column eluted with Cyclohexane/EtOAc (from 100:0 to 80:20 Cyclohexane/EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into 184.4 ml (1.494 mol) of N-methylformanilide were added dropwise, with cooling, 130.9 ml (1.404 mol) of phosphoryl chloride over a period of 20 minutes. The mixture was allowed to warm to room temperature and stirred for one hour. Ortho-tertbutylphenol (138.2 ml; 0.9 mol) was then added dropwise to the reaction solution over a period of 25 minutes. After phenol addition was complete, the resulting reaction mixture was stirred for an additional 30 minutes at room temperature and then heated to approximately 60° C. and stirred for five hours at that temperature. The reaction mixture was poured into a volume of crushed ice and extracted with chloroform. The aqueous layer was separated and washed again with chloroform. The chloroform layers were combined and extracted with 2000 ml of a 5% potassium hydroxide solution. The aqueous potassium hydroxide extract was then added to 1000 ml of chloroform. The pH of the resulting two-phase mixture was adjusted to approximately pH 2.0 with concentrated hydrochloric acid. The mixture's layers were separated and the aqueous layer was again extracted with chloroform. The organic layer from the two-phase mixture and the chloroform extract were combined, washed with water and then dried over sodium sulfate. The volatile components of the solution were removed under reduced pressure to provide a residue. This residue was dissolved in 100 ml of hot toluene and the resulting solution was diluted with 100 ml of hexanes. The solution was slowly cooled to room temperature while a precipitate formed. This precipitate was recovered by filtration, washed with hexanes and then dried under vacuum to provide 20.0 g of the desired subtitled intermediate. with cooling the resulting reaction mixture was stirred for an additional 30 minutes at room temperature heated to approximately 60° C. stirred for five hours at that temperature The reaction mixture was poured into a volume of crushed ice extracted with chloroform The aqueous layer was separated washed again with chloroform extracted with 2000 ml of a 5% potassium hydroxide solution The aqueous potassium hydroxide extract was then added to 1000 ml of chloroform The mixture's layers were separated the aqueous layer was again extracted with chloroform The organic layer from the two-phase mixture and the chloroform extract washed with water dried over sodium sulfate The volatile components of the solution were removed under reduced pressure to provide a residue The solution was slowly cooled to room temperature while a precipitate formed This precipitate was recovered by filtration washed with hexanes dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into 101.5 g of N-methylformanilide was added dropwise with cooling 107 g of phosphoryl chloride over a period of 15 minutes. The mixture was allowed to warm to room temperature and stirred for 70 minutes. 67.5 g of ortho-t-butylphenol was added and stirred for about 45 minutes after which the mixture was heated to about 50-60° C. and allowed to stir for 4.5 hours. The reaction mixture was poured into a volume of crushed ice and extracted with chloroform. The aqueous layer was separated and washed again with chloroform. The chloroform layers were combined and extracted with 2000 ml of a 5% potassium hydroxide solution. The aqueous potassium hydroxide layer was separated and added to 1000 ml of chloroform. The pH of the resulting two-phase mixture was adjusted to 3 with concentrated hydrochloric acid with stirring. The resultant layers were separated and the aqueous layer was again extracted with chloroform and dried over sodium sulfate overnight to give 18.1 g of the desired subtitled intermediate. stirred for about 45 minutes after which the mixture was heated to about 50-60° C. to stir for 4.5 hours The reaction mixture was poured into a volume of crushed ice extracted with chloroform The aqueous layer was separated washed again with chloroform extracted with 2000 ml of a 5% potassium hydroxide solution The aqueous potassium hydroxide layer was separated added to 1000 ml of chloroform with stirring The resultant layers were separated the aqueous layer was again extracted with chloroform dried over sodium sulfate overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into 101.5 g of N-methylformanilide was added dropwise with cooling 107 g of phosphoryl chloride over a period of 15 minutes. The mixture was allowed to warm to room temperature and stirred for 70 minutes. 67.5 g of ortho-t-butylphenol was added and stirred for about 45 minutes after which the mixture was heated to about 50-60° C. and allowed to stir for 4.5 hours. The reaction mixture was poured into a volume of crushed ice and extracted with chloroform. The aqueous layer was separated and washed again with chloroform. The chloroform layers were combined and extracted with 2000 ml of a 5% potassium hydroxide solution. The aqueous potassium hydroxide layer was separated and added to 1000 ml of chloroform. The pH of the resulting two-phase mixture was adjusted to 3 with concentrated hydrochloric acid with stirring. The resultant layers were separated and the aqueous layer was again extracted with chloroform and dried over sodium sulfate overnight to give 18.1 g of the desired subtitled intermediate. stirred for about 45 minutes after which the mixture was heated to about 50-60° C. to stir for 4.5 hours The reaction mixture was poured into a volume of crushed ice extracted with chloroform The aqueous layer was separated washed again with chloroform extracted with 2000 ml of a 5% potassium hydroxide solution The aqueous potassium hydroxide layer was separated added to 1000 ml of chloroform with stirring The resultant layers were separated the aqueous layer was again extracted with chloroform dried over sodium sulfate overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Chlorine gas was passed into a solution of 3-tert-butyl-4-hydroxybenzaldehyde (2.5 gm) in acetic acid (20 ml) for 1 hour. The solution was poured into water and the product collected. Recrystallisation from aqueous ethanol gave 3-tert-butyl-5-chloro-4-hydroxybenzaldehyde m.p. 123° C. the product collected Recrystallisation from aqueous ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Chlorine gas was passed into a solution of 3-tert-butyl-4-hydroxybenzaldehyde (2.5 gm) in acetic acid (20 ml) for 1 hour. The solution was poured into water and the product collected. Recrystallisation from aqueous ethanol gave 3-tert-butyl-5-chloro-4-hydroxybenzaldehyde m.p. 123° C. the product collected Recrystallisation from aqueous ethanol