4-tert-butyl-3-chlorophenol

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

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of potassium carbonate (994 mg, 7.2 mmol) and 4-tert-butyl-3-chlorophenol (440 mg, 2.4 mmol) in acetone (5 ml) was added t-butyl bromoacetate (370 mg, 1.9 mmol) was added and the mixture was refluxed at 60° C. for 14 hours. Filtrating of potassium carbonate, evaporation, and purification through silica gel column chromatography eluting with hexane/EtOAc (20:1 to 10:1) to furnish the tert-butyl (4-tert-butyl-3-chlorophenoxy)acetate (720 mg, 100%). The mixture of tert-butyl (4-tert-butyl-3-chlorophenoxy)acetate (720 mg, 2.4 mmol), TFA (2.0 ml), DCM (2.0 ml) was stirred for 5 hours at room temperature. After being concentrated in vacuo, the residue was triturated with hexane to furnish the title compound (582 mg, 100%) as a white solid. 1H NMR (300 MHz, CDCl3): δ 1.45 (9H, s), 4.67 (2H, s), 6.76 (1H, dd, J=2.6, 8.6 Hz), 6.96 (1H, d, J=2.6 Hz), 7.35 (1H, d, J=8.6 Hz). was added Filtrating of potassium carbonate, evaporation, and purification through silica gel column chromatography eluting with hexane/EtOAc (20:1 to 10:1)

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

Procedure: A mixture of 9.65 g (52.2 mmol) of 3-chloro-4-(1,1-dimethylethyl)phenol and 7.37 g (52.2 mmol) of hexamethylenetetramine was refluxed in 150 ml of trifluoroacetic acid for 3 hours. The solution was cooled to ambient temperature and diluted with 500 ml of water. The aqueous residue was extracted with ether. The organic phase was washed with saturated sodium bicarbonate solution, dried and evaporated. The residue was chromatographed on 250 g of silica gel using a gradient from hexane to 20:80 (v/v) ether: hexane as eluent. There was obtained 1.87 g (8.79 mmol, 17%) of 2-hydroxy-4-chloro-5-(1,1-dimethylethyl)benzaldehyde; mp 38°-39° C. The aqueous residue was extracted with ether The organic phase was washed with saturated sodium bicarbonate solution dried evaporated The residue was chromatographed on 250 g of silica gel using a gradient from hexane to 20:80 (v/v) ether

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an acetone (5 ml) solution of 4-tert-butyl-3-chlorophenol (440 mg, 2.4 mmol) were added potassium carbonate (994 mg, 7.2 mmol) and tert-butyl bromoacetate (0.7 ml, 4.8 mmol). The stirred mixture was refluxed at 65° C. for 14 hours. The precipitate was filtered off and washed with acetone. The filtrate was concentrated under reduced pressure to give a residue, which was applied to a silica gel chromatography column and eluted with ethyl acetate/hexane= 1/9 to furnish 0.83 g (100% yield) of the title as a colorless oil. The precipitate was filtered off washed with acetone The filtrate was concentrated under reduced pressure to give a residue, which eluted with ethyl acetate/hexane= 1/9 to furnish 0.83 g (100% yield) of the title as a colorless oil

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-tert-Butyl-3-chloroaniline (690 mg, 3.8 mmol) was dissolved in 12 M sulfuric acid (30 ml) and then heated at 90° C. To the clear solution was added 5 ml of aqueous solution of sodium nitrite (776 mg, 11.3 mmol) at ambient temperature. The reaction mixture was stirred at ambient temperature for 15 minutes. Urea was added to the mixture until excess sodium nitrite was destroyed (by checking starch-iodine test paper). A small amount of cupric sulfate was added to the mixture and then the mixture was stirred at 90° C. for 30 minutes. The resulting organic layer was extracted with ethyl acetate washed with brine, dried over sodium sulfate. After filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give a residue, which was applied to a silica gel chromatography column and eluted with ethyl acetate/hexane=¼ to furnish 0.44 g (64% yield) of the title compound as a brown oil. was destroyed (by checking starch-iodine test paper) A small amount of cupric sulfate was added to the mixture the mixture was stirred at 90° C. for 30 minutes The resulting organic layer was extracted with ethyl acetate washed with brine dried over sodium sulfate After filtration to separate solvent and sodium sulfate the solvent was removed under reduced pressure to give a residue, which eluted with ethyl acetate/hexane=¼

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

Procedure: A mixture of 50 g (0.39 mol) of 3-chlorophenol in 250 ml of hexane and 125 ml of 85% phosphoric acid was heated to reflux. A solution of 43.2 g (0.584 mol) of 2-methyl-2-propanol in 25 ml of hexane was added over 1.5 hours. After addition, the reaction mixture was refluxed for 4 hours. The organic phase was separated and extracted four times with 30 ml of lN sodium hydroxide solution. The combined aqueous fractions were made acidic and extracted with methylene chloride. The organic phase was dried and evaporated at 90° C. (25 mm). The residue was crystallized from hexane. There was obtained 0.46 g (2.49 mmol, 0.6%) of 3-chloro-4-(1,1-dimethylethyl)phenol as a white solid after crystallization from hexane; mp 65°-67° C. was heated to reflux After addition the reaction mixture was refluxed for 4 hours The organic phase was separated extracted four times with 30 ml of lN sodium hydroxide solution extracted with methylene chloride The organic phase was dried evaporated at 90° C. (25 mm) The residue was crystallized from hexane