3-propan-2-yloxyphenol

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

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-[(1-methylethyl)oxy]phenol (Intermediate 27, 456 mg) in DMSO (8 mL) was added t-BuOK (336 mg, 3 mmol, Acros). The reaction mixture was stirred at 20° C. for 30 minutes. 2-chloro-5-nitropyridine (474 mg, 3 mmol, Aldrich) was added and the resulting mixture was stirred at 120° C. for 2 hours. The reaction mixture was cooled to room temperature, poured into ice-water (50 mL) and extracted with dichloromethane (3 times 50 mL). The combined organic layers were dried over sodium sulphate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with (PE:EtOAc=50:1) to afford the title compound as a light yellow solid (670 mg). the resulting mixture was stirred at 120° C. for 2 hours The reaction mixture was cooled to room temperature extracted with dichloromethane (3 times 50 mL) The combined organic layers were dried over sodium sulphate filtered concentrated The residue was purified by column chromatography on silica gel eluting with (PE:EtOAc=50:1)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-[(1-methylethyl)oxy]phenol (Intermediate 27, 456 mg) in DMSO (8 mL) was added t-BuOK (336 mg, 3 mmol, Acros). The reaction mixture was stirred at 20° C. for 30 minutes. 2-chloro-5-nitropyridine (474 mg, 3 mmol, Aldrich) was added and the resulting mixture was stirred at 120° C. for 2 hours. The reaction mixture was cooled to room temperature, poured into ice-water (50 mL) and extracted with dichloromethane (3 times 50 mL). The combined organic layers were dried over sodium sulphate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with (PE:EtOAc=50:1) to afford the title compound as a light yellow solid (670 mg). the resulting mixture was stirred at 120° C. for 2 hours The reaction mixture was cooled to room temperature extracted with dichloromethane (3 times 50 mL) The combined organic layers were dried over sodium sulphate filtered concentrated The residue was purified by column chromatography on silica gel eluting with (PE:EtOAc=50:1)

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

Procedure: To a solution of 1,3-benzenediol (8 g, 72.7 mmol) and 2-iodopropane (12 g, 70.6 mmol) in ethanol (100 mL preheated at reflux) was added a solution of KOH (83%, 5.3 g, 77.6 mmol) in water (20 mL) over a period of 30 minutes. The mixture was refluxed for 3 hours and poured into NaOH (1 N, 100 mL). The resulting mixture was extracted with ethyl acetate (3 times 50 mL) and the aqueous layer was acidified with 10% HCl to adjust the pH=5 and extracted with ethyl acetate (3 times 50 mL). The combined extracts were washed with brine (50 mL), dried and concentrated under vacuum. The residue was purified by column chromatography on silica gel (PE:EtOAc=5:1) to afford the title compound as a colourless oil (2.1 g). The mixture was refluxed for 3 hours The resulting mixture was extracted with ethyl acetate (3 times 50 mL) extracted with ethyl acetate (3 times 50 mL) The combined extracts were washed with brine (50 mL) dried concentrated under vacuum The residue was purified by column chromatography on silica gel (PE:EtOAc=5:1)

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

Procedure: In 10 ml of THF, 1.5 g of resorcinol was dissolved and 2.24 ml of DBU was added under ice cooling. The resultant mixture was stirred for 10 min at room temperture. To the mixture, 1.92 ml of isopropyl bromide was added and refluxed for 2 hr. The reaction mixture was neutralized with acetic acid and evaporated under reduced pressure. The evaporated residue was redissolved in ethyl acetate and washed with 5% aqueous citric acid solution and saturated aqueous sodium chloride solution, successively, and dried over anhydrous sodium sulfate. The dried solution was evaporated under reduced pressure and the residue was subjected to a silica gel column chromatography (chloroform:methanol=40:1) to give 466 mg of the title compound. refluxed for 2 hr evaporated under reduced pressure The evaporated residue was redissolved in ethyl acetate washed with 5% aqueous citric acid solution and saturated aqueous sodium chloride solution successively, and dried over anhydrous sodium sulfate The dried solution was evaporated under reduced pressure

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

Procedure: In 10 ml of THF, 1.5 g of resorcinol was dissolved and 2.24 ml of DBU was added under ice cooling. The resultant mixture was stirred for 10 min at room temperture. To the mixture, 1.92 ml of isopropyl bromide was added and refluxed for 2 hr. The reaction mixture was neutralized with acetic acid and evaporated under reduced pressure. The evaporated residue was redissolved in ethyl acetate and washed with 5% aqueous citric acid solution and saturated aqueous sodium chloride solution, successively, and dried over anhydrous sodium sulfate. The dried solution was evaporated under reduced pressure and the residue was subjected to a silica gel column chromatography (chloroform:methanol=40:1) to give 466 mg of the title compound. refluxed for 2 hr evaporated under reduced pressure The evaporated residue was redissolved in ethyl acetate washed with 5% aqueous citric acid solution and saturated aqueous sodium chloride solution successively, and dried over anhydrous sodium sulfate The dried solution was evaporated under reduced pressure

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

Procedure: To a mixture of 3-hydroxyphenol (20.0 g, 0.182 mmoL), 2-iodopropane (30.9 g, 0.182 mmoL) in ethanol (25 mL) at refluxing was added KOH (88%, 12.2 g, 0.191 mmoL) in water (30 mL) over a period of 60 min. The resulting mixture was refluxed for 3 hours. The mixture was poured into 1N NaOH and extracted with ether (1×). The aqueous layer was acidified with 10% HCl to pH 5 and extracted with ether (2×). The combined extracts were washed with brine (1×), dried over MgSO4 and concentrated. The residue was purified on silica gel eluting with ethyl acetate:hexane (1:8) to give the desired product as a colorless liquid (11.7 g, 43%). This was used directly in the next step. 1H NMR (500 MHz, CDCl3) δ ppm 7.10 (t, 1H) 6.47 (d, J=7.32 Hz, 1H) 6.36-6.42 (m, 1H) 4.70 (s, 1H) 4.45-4.55 (m, 1H) 4.13 (q, J=7.32 Hz, 1H) 1.32 (d, 6H). MS m/z (DCI) 153.0 (M+H)+. at refluxing The resulting mixture was refluxed for 3 hours extracted with ether (1×) extracted with ether (2×) The combined extracts were washed with brine (1×) dried over MgSO4 concentrated The residue was purified on silica gel eluting with ethyl acetate:hexane (1:8)

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

Procedure: To a mixture of 3-hydroxyphenol (20.0 g, 0.182 mmoL), 2-iodopropane (30.9 g, 0.182 mmoL) in ethanol (25 mL) at refluxing was added KOH (88%, 12.2 g, 0.191 mmoL) in water (30 mL) over a period of 60 min. The resulting mixture was refluxed for 3 hours. The mixture was poured into 1N NaOH and extracted with ether (1×). The aqueous layer was acidified with 10% HCl to pH 5 and extracted with ether (2×). The combined extracts were washed with brine (1×), dried over MgSO4 and concentrated. The residue was purified on silica gel eluting with ethyl acetate:hexane (1:8) to give the desired product as a colorless liquid (11.7 g, 43%). This was used directly in the next step. 1H NMR (500 MHz, CDCl3) δ ppm 7.10 (t, 1H) 6.47 (d, J=7.32 Hz, 1H) 6.36-6.42 (m, 1H) 4.70 (s, 1H) 4.45-4.55 (m, 1H) 4.13 (q, J=7.32 Hz, 1H) 1.32 (d, 6H). MS m/z (DCI) 153.0 (M+H)+. at refluxing The resulting mixture was refluxed for 3 hours extracted with ether (1×) extracted with ether (2×) The combined extracts were washed with brine (1×) dried over MgSO4 concentrated The residue was purified on silica gel eluting with ethyl acetate:hexane (1:8)

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

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

Procedure: 3-Isopropoxyphenol (80 mg, 0.53 mmol) and 2-chloro-oxazole-4-carboxylic acid [1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-amide (35 mg, 0.09 mmol) was reacted using K2CO3 (60 mg, 0.43 mmol) as described above to give the title compound (28 mg, 61%) after purification by flash chromatography on silica gel (hexane: EtOAc=1:1).

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-[(1-methylethyl)oxy]phenol (Intermediate 27, 456 mg) in DMSO (8 mL) was added t-BuOK (336 mg, 3 mmol, Acros). The reaction mixture was stirred at 20° C. for 30 minutes. 2-chloro-5-nitropyridine (474 mg, 3 mmol, Aldrich) was added and the resulting mixture was stirred at 120° C. for 2 hours. The reaction mixture was cooled to room temperature, poured into ice-water (50 mL) and extracted with dichloromethane (3 times 50 mL). The combined organic layers were dried over sodium sulphate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with (PE:EtOAc=50:1) to afford the title compound as a light yellow solid (670 mg). the resulting mixture was stirred at 120° C. for 2 hours The reaction mixture was cooled to room temperature extracted with dichloromethane (3 times 50 mL) The combined organic layers were dried over sodium sulphate filtered concentrated The residue was purified by column chromatography on silica gel eluting with (PE:EtOAc=50:1)

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

Procedure: To a solution of 1,3-benzenediol (8 g, 72.7 mmol) and 2-iodopropane (12 g, 70.6 mmol) in ethanol (100 mL preheated at reflux) was added a solution of KOH (83%, 5.3 g, 77.6 mmol) in water (20 mL) over a period of 30 minutes. The mixture was refluxed for 3 hours and poured into NaOH (1N, 100 mL). The resulting mixture was extracted with ethyl acetate (3 times 50 mL) and the aqueous layer was acidified with 10% HCl to adjust the pH=5 and extracted with ethyl acetate (3 times 50 mL). The combined extracts were washed with brine (50 mL), dried and concentrated under vacuum. The residue was purified by column chromatography on silica gel (PE:EtOAc=5:1) to afford the title compound as a colourless oil (2.1 g). The mixture was refluxed for 3 hours The resulting mixture was extracted with ethyl acetate (3 times 50 mL) extracted with ethyl acetate (3 times 50 mL) The combined extracts were washed with brine (50 mL) dried concentrated under vacuum The residue was purified by column chromatography on silica gel (PE:EtOAc=5:1)