2',4'-Dihydroxypropiophenone

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: A mixture of 2′,4′-dihydroxy-propiophenone (24.9 g, 0.15 mol), 3-bromo-propyne (24.2 g, 0.20 mol) and K2CO3 (20.7 g, 0.15 mol) in acetone (500 mL) was refluxed for 12 h. The reaction mixture was allowed assume room temperature and the precipitate was removed by filtration. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O), to give 26.2 g (85%) of 1-(2-hydroxy-4-prop-2-ynyloxy-phenyl)-propan-1-one. was refluxed for 12 h was allowed assume room temperature the precipitate was removed by filtration The filtrate was concentrated under reduced pressure The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O)

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

Procedure: A mixture of 2′,4′-dihydroxy-propiophenone (24.9 g, 0.15 mol), 3-bromo-propyne (24.2 g, 0.20 mol) and K2CO3 (20.7 g, 0.15 mol) in acetone (500 mL) was refluxed for 12 h. The reaction mixture was allowed assume room temperature and the precipitate was removed by filtration. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O), to give 26.2 g (85%) of 1-(2-hydroxy-4-prop-2-ynyloxy-phenyl)-propan-1-one. was refluxed for 12 h was allowed assume room temperature the precipitate was removed by filtration The filtrate was concentrated under reduced pressure The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O)

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

Procedure: A mixture of 2′,4′-dihydroxy-propiophenone (24.9 g, 0.15 mol), 3-bromo-propyne (24.2 g, 0.20 mol) and K2CO3 (20.7 g, 0.15 mol) in acetone (500 mL) was refluxed for 12 h. The reaction mixture was allowed assume room temperature and the precipitate was removed by filtration. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O), to give 26.2 g (85%) of 1-(2-hydroxy-4-prop-2-ynyloxy-phenyl)-propan-1-one. was refluxed for 12 h was allowed assume room temperature the precipitate was removed by filtration The filtrate was concentrated under reduced pressure The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O)

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

Procedure: 6.00 g of 2′,4′-dihydroxypropiophenone was dissolved in 70 ml of acetone. Thereafter, 7.09 g of potassium carbonate and 3.03 ml of methyl iodide were successively added to the reaction solution. The reaction solution was then heated to reflux. Approximately 3 hours later, the reaction solution was stood to cool and then filtered. The filtrate was concentrated under a reduced pressure. A saturated sodium chloride solution and ethyl acetate were added to the residue, so as to separate an organic layer. The obtained organic layer was washed with 2 N hydrochloric acid and a saturated sodium chloride solution, and then dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure. The residue was solidified from hexane-ethyl acetate, so as to obtain 5.64 g of the subject compound. 1H-NMR (CDCl3) δ (ppm): 1.23 (t, J=7.2 Hz, 3H), 2.95 (q, J=7.2 Hz, 2H), 3.83 (s, 3H), 6.40-6.45 (m, 2H), 7.65 (dd, J=1.6 Hz, 8.0 Hz, 1H), 12.8 (s, 1H). The reaction solution was then heated to reflux Approximately 3 hours to cool filtered The filtrate was concentrated under a reduced pressure A saturated sodium chloride solution and ethyl acetate were added to the residue so as to separate an organic layer The obtained organic layer was washed with 2 N hydrochloric acid a saturated sodium chloride solution, and then dried over anhydrous magnesium sulfate After removing the drying agent by filtration the organic layer was concentrated under a reduced pressure

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

Procedure: 6.00 g of 2′,4′-dihydroxypropiophenone was dissolved in 70 ml of acetone. Thereafter, 7.09 g of potassium carbonate and 3.03 ml of methyl iodide were successively added to the reaction solution. The reaction solution was then heated to reflux. Approximately 3 hours later, the reaction solution was stood to cool and then filtered. The filtrate was concentrated under a reduced pressure. A saturated sodium chloride solution and ethyl acetate were added to the residue, so as to separate an organic layer. The obtained organic layer was washed with 2 N hydrochloric acid and a saturated sodium chloride solution, and then dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the organic layer was concentrated under a reduced pressure. The residue was solidified from hexane-ethyl acetate, so as to obtain 5.64 g of the subject compound. 1H-NMR (CDCl3) δ (ppm): 1.23 (t, J=7.2 Hz, 3H), 2.95 (q, J=7.2 Hz, 2H), 3.83 (s, 3H), 6.40-6.45 (m, 2H), 7.65 (dd, J=1.6 Hz, 8.0 Hz, 1H), 12.8 (s, 1H). The reaction solution was then heated to reflux Approximately 3 hours to cool filtered The filtrate was concentrated under a reduced pressure A saturated sodium chloride solution and ethyl acetate were added to the residue so as to separate an organic layer The obtained organic layer was washed with 2 N hydrochloric acid a saturated sodium chloride solution, and then dried over anhydrous magnesium sulfate After removing the drying agent by filtration the organic layer was concentrated under a reduced pressure

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

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

Procedure: The title compound was prepared in a similar manner to 1-(3-chloro-2,4-dihydroxy-phenyl)-ethanone (Preparation 3) employing 2,4-dihydroxypropiophenone to give 4.5 g, 37% of an off-white solid. LCMS 1 201 M+.

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 12 L round bottom flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet was charged with of sodium hydroxide (440 g, 11 moles) and 4.5 L of distilled water. Sodium borohydride (440 g, 11.6 moles) was added and the batch was held at 50° C. until all the solids dissolved. To the mixture there was added 2,4-dihydroxypropiophenone (440 g, 2.6 moles) resulting in a 10-15° C. exotherm and some hydrogen evolution. The batch was held at 80° C. for 90 minutes then cooled to 10-20° C. in an ice bath. Hydrogen evolution was observed during the 90 minute hold at 80° C. 1.9 kg of hydrochloric acid (37%) was added drop-wise (hydrogen evolution) bringing the batch to pH 6. The product was extracted into methylene chloride (5×500 mL). The methylene chloride was stripped off and replaced with toluene (2 L). The product was crystallized from toluene to give propyl resorcinol (261.5 g, 1.7 mol, 65% yield). A 12 L round bottom flask equipped with a mechanical stirrer reflux condenser and nitrogen inlet was held at 50° C. until all dissolved resulting in a 10-15° C. exotherm was observed during the 90 minute hold at 80° C The product was extracted into methylene chloride (5×500 mL) The product was crystallized from toluene

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

Procedure: A mixture of 2′,4′-dihydroxy-propiophenone (24.9 g, 0.15 mol), 3-bromo-propyne (24.2 g, 0.20 mol) and K2CO3 (20.7 g, 0.15 mol) in acetone (500 mL) was refluxed for 12 h. The reaction mixture was allowed assume room temperature and the precipitate was removed by filtration. The filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O), to give 26.2 g (85%) of 1-(2-hydroxy-4-prop-2-ynyloxy-phenyl)-propan-1-one. was refluxed for 12 h was allowed assume room temperature the precipitate was removed by filtration The filtrate was concentrated under reduced pressure The crude product was purified by column chromatography (silica gel, 0→2% MeOH in H2O)

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