2-propylbenzene-1,3-diol

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

Procedure: To a solution of 2-propyl resorcinol (178.27 g; 1.171 mol) in dry DMF (1200 mL) was added cesium carbonate (104.95 g; 322.12 mmol). The mixture was stirred at room temperature and treated dropwise with a solution of 2-bromoacetophenone (58.29 G; 292.84 mmol) in dry DMF (500 mL) over 2 hours. The was stirred at ambient temperature for 64 hours. The reaction mixture was partitioned between isopropyl acetate and water. The aqueous was adjusted to pH 13 by addition of aq. 5N sodium hydroxide. The organic was dried over magnesium sulfate, filtered and evaporated to a residue. The residue was dissolved in methylene chloride (110 mL) and hexane (350 mL) and heated to reflux. The solution was cooled to -10° C. Stirring was continued for 1 hour. The title compound was recovered by filtration. The was stirred at ambient temperature for 64 hours The reaction mixture was partitioned between isopropyl acetate and water The aqueous was adjusted to pH 13 by addition of aq. 5N sodium hydroxide The organic was dried over magnesium sulfate filtered evaporated to a residue The residue was dissolved in methylene chloride (110 mL) hexane (350 mL) and heated to reflux The solution was cooled to -10° C Stirring The title compound was recovered by filtration

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

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

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4,-Dimethoxy-3-propylbenzene (7.2 g, 39.94 mmol) was dissolved in 50 ml methylene chloride and the solution was cooled to -70° C. then 87.0 ml of 1M boron tribromide in methylene chloride was added over a period of 1 hour. The reaction mixture was stirred at -70° C. for 1 hour, then at room temperature for 2 hours. The reaction mixture was poured into 250 ml of ice water very slowly. This mixture was extracted 3 times with 100 ml methylene chloride. The extracts were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under vacuum to give the product as a white solid (4.9 g, 81.7%). at room temperature for 2 hours This mixture was extracted 3 times with 100 ml methylene chloride dried over anhydrous magnesium sulfate filtered the solvent was removed under vacuum

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4,-Dimethoxy-3-propylbenzene (7.2 g, 39.94 mmol) was dissolved in 50 ml methylene chloride and the solution was cooled to -70° C. then 87.0 ml of 1 M boron tribromide in methylene chloride was added over a period of 1 hour. The reaction mixture was stirred at -70° C. for 1 hour, then at room temperature for 2 hours. The reaction mixture was poured into 250 ml of ice water very slowly. This mixture was extracted 3 times with 100 ml methylene chloride. The extracts were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under vacuum to give the product as a white solid (4.9 g, 81.7%). at room temperature for 2 hours This mixture was extracted 3 times with 100 ml methylene chloride dried over anhydrous magnesium sulfate filtered the solvent was removed under vacuum

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

Procedure: Sodium hydride (1.08 g of a 60% oil dispersion, 27 mmoles) under an argon atmosphere was washed with 15 ml of dry hexane. The hexane supernatant was removed via syringe. Dry tetrahydrofuran (60 ml) was added to the sodium hydride and, with stirring at room temperature, the 2-propyl-1,3-dihydroxybenzene (4.08 g, 27 mmoles) was added as a 40 ml tetrahydrofuran solution. After stirring at room temperature for 25 minutes, the ethyl 2-bromopropionate (4.64 g, 26 mmoles) was added rapidly. After stirring at room temperature for 17 hours, the reaction was quenched with a saturated aqueous ammonium chloride solution and the tetrahydrofuran was removed under vacuum. The resulting aqueous mixture was extracted several times with ethyl acetate. The organic extract was dried over magnesium sulfate. Filtration and solvent removal gave an orange oil. This oil was purified by flash chromatography on silica gel eluting with 20% ethyl acetate/hexane. The desired title ester was obtained as a white solid (2.43 g, 36%). Sodium hydride (1.08 g of a 60% oil dispersion, 27 mmoles) under an argon atmosphere was washed with 15 ml of dry hexane The hexane supernatant was removed via syringe Dry tetrahydrofuran (60 ml) was added to the sodium hydride After stirring at room temperature for 25 minutes After stirring at room temperature for 17 hours the reaction was quenched with a saturated aqueous ammonium chloride solution the tetrahydrofuran was removed under vacuum The resulting aqueous mixture was extracted several times with ethyl acetate The organic extract was dried over magnesium sulfate Filtration and solvent removal gave an orange oil This oil was purified by flash chromatography on silica gel eluting with 20% ethyl acetate/hexane

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of solid 1,3-dimethoxy-2-propylbenzene (33.70 g, 190 mmoles) and solid pyridine hydrochloride (150 g, 1.30 mole) was warmed to 180° C. After 7.5 hours the reaction was cooled to 110° C. and 50 ml of water was added slowly. After the reaction cooled to room temperature, it was diluted with 100 ml of water and extracted several times with ethyl acetate. The ethyl acetate extract was washed once with 2N hydrochloric acid and then dried over magnesium sulfate. Filtration and solvent removal gave 38.5 g of an orange solid. The title product was purified by recrystallization from dichloromethane providing 11.86 g (41%) of yellow crystals. After 7.5 hours the reaction was cooled to 110° C. After the reaction cooled to room temperature extracted several times with ethyl acetate The ethyl acetate extract was washed once with 2N hydrochloric acid dried over magnesium sulfate Filtration and solvent removal

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of solid 1,3-dimethoxy-2-propylbenzene (33.70 g, 190 mmol) and solid pyridine hyrochloride (150 g, 1.30 mol) were warmed to 180° C. After 7.5 hours, the reaction was cooled to 110° C. and 50 mL of H2O was added slowly. After the reaction cooled to room temperature, it was diluted with 100 mL of water and extracted several times with EtOAc. The EtOAc extract was washed once with 2N HCl and then dried over MgSO4. Filtration and solvent removal gave 38.5 g of an orange solid. The product was purified by recrystallization from dichloromethane providing 11.86 g (41%) of yellow crystals. the reaction was cooled to 110° C. After the reaction cooled to room temperature extracted several times with EtOAc The EtOAc extract was washed once with 2N HCl dried over MgSO4 Filtration and solvent removal

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

Procedure: 2-Propyl resorcinol (1.50 g, 9.86 mmol) was dissolved in DMF (anhydrous, 20 mL) and K2CO3 (681 mg, 4.93 mmol) was added. After stirring for 10 min at rt, iodomethane (0.92 mL, 14.8 mmol) was added and the reaction mixture was stirred for 6 h at 60° C. After cooling to rt, the reaction mixture was acidified with HCl (1 N aqueous solution) and concentrated under reduced pressure. Water was added and the aqueous phase was extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc/hexane (v/v) 1:15) gave 33 mg (24%) of the title compound as an oil. 1H NMR (400 MHz, CDCl3): δ 0.97 (t, 3H), 1.54 (m, 2H), 2.61 (t, 2H), 3.81 (s, 3H), 4.68 (br, 1H), 6.47 (m, 2H), 7.03 (t, 1H). the reaction mixture was stirred for 6 h at 60° C After cooling to rt concentrated under reduced pressure Water was added the aqueous phase was extracted with EtOAc (2×) The combined organic phases were dried over Na2SO4 filtered concentrated under reduced pressure Purification by silica gel flash chromatography (EtOAc/hexane (v/v) 1:15)