1-(4-hydroxyphenyl)-2-phenylbutan-1-one

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

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

Conditions: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.4 G. (0.10 mole) 1-(4'-methoxyphenyl)-2-phenyl-n-butan-1-one and 34.5 g. (0.30 mole) pyridine hydrochloride are melted and refluxed at 220° C. for one hour while being agitated. The melt while still liquid is poured into ice water and the precipitate dissolved in 400 ml. ether. After washing the etheric solution with water, it is shaken out with 1 N sodium hydroxide solution. The aqueous alkaline solution is acidified with 5 N hydrochlc.ric acid and extracted with 500 ml. ether. The organic phase is washed with water and dried over sodium sulfate. The solvent is removed in vacuo and the crude product is crystallized from dilute ethanol. Obtained are colorless crystals having a melting point of 131° C.; Rf 0.45 [toluene/ethyl acetate (9/1)]; yield: 16.3 g. (68%). the precipitate dissolved in 400 ml After washing the etheric solution with water, it is shaken out with 1 N sodium hydroxide solution extracted with 500 ml The organic phase is washed with water dried over sodium sulfate The solvent is removed in vacuo the crude product is crystallized from dilute ethanol Obtained

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

Procedure: 4-(β-Dimethylaminoethoxy)-α-ethyldesoxybenzoin (b.p. 162° C./0.075 mm.) may be obtained from α-ethyl-4-hydroxydesoxybenzoin by an analogous procedure to that described below for the preparation of 4-(β-dimethylaminoethoxy)-α-methyldesoxybenzoin, and α-ethyl-4-hydroxydesoxybenzoin itself (m.p. 122°-124° C.) may be obtained from α-ethyl-4-methoxydesoxybenzoin by an analogous procedure to that described below for the preparation of 4-hydroxy-α-methyldesoxybenzoin.

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

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

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of compound 8 (908 g, 3.78 mol) in 1,2-dichloroethane (6.36 L) stirred at 30° C. was treated with dihydropyran (1590 g, 18.9 mol) in a single portion. The resulting solution was treated with CaCl2 (83.8 g, 0.76 mmol) in a single portion and the reaction warmed at 70° C. for 16 h. The reaction was filtered through celite and the solid washed with 1,2-dichloroethane (2×900 mL). The filtrate was concentrated by distillation to approximately 5 L and heptane added (9 L). The reaction solution was again concentrated by distillation to approximately 7 L and then cooled slowly and held at 5° C. for 1 h. The solids were filtered, washed with heptane (2×1.8 L) and dried in vacuo at 40° C. to afford 1134 g (93%) of 9 as a solid. 1HNMR (400 MHz, DMSO-d6): δ 0.79 (t, J=7.3 Hz, 3H), 1.49-1.83 (m, 8H), 2.03 (h, J=7.0 Hz, 1H), 3.49-3.66 (m, 2H), 4.65 (t, J=7.2 Hz, 1H), 7.02 (d, J=8.4 Hz, 2H), 7.13-7.30 (m, 5H), 7.97 (d, J=8.4 Hz, 2H). the reaction warmed at 70° C. for 16 h The reaction was filtered through celite the solid washed with 1,2-dichloroethane (2×900 mL) The filtrate was concentrated by distillation to approximately 5 L and heptane added (9 L) The reaction solution was again concentrated by distillation to approximately 7 L cooled slowly The solids were filtered washed with heptane (2×1.8 L) dried in vacuo at 40° C.

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 5.0 L round bottom flask was charged with 164.2 (1.00 mol) (±)-2-phenylbutyric acid (III) and 110.3 g (1.02 mol) anisole and anhydrous toluene (575 mL) and stirred until dissolved. The resulting solution was cooled to 10° C. and 367.5 g (1.75 mol) TFAA added such that the temperature did not rise above 15° C. The solution was heated to 35° C. for 1 h then at 40° C. for 72 h. The solution was cooled to 20° C. and toluene (1300 mL) added followed by 2N NaOH (1.80 mol) with external cooling and vigorous stirring at a rate such that the reaction temperature did not rise above 35° C. The mixture was stirred for 1 h and the pH then adjusted to 10 by addition of 2N NaOH. The aqueous layer was removed and the upper organic layer was washed with H2O (900 mL). The aqueous layer was removed and the toluene layer concentrated to ˜1000 mL via atmospheric distillation. This solution was then quickly added to a stirred mixture of 266.7 g AlCl3 (2.00 mol) and anhydrous toluene (900 mL) at 70° C. The solution was stirred at 70° C. for 1 h, cooled to 15° C., and then added to water (1000 mL, 15° C.) with cooling such that the temperature did not exceed 40° C. After complete addition and cooling to 25° C., EtOAc (900 mL) was added and then stirred for 5 minutes. The lower aqueous layer was removed and the organic layer washed with water (1000 mL). The organic layer was concentrated under reduced pressure (˜60° C.) to ˜1000 mL. The solution was then cooled to 50° C. and hexanes (660 mL) added while maintaining an internal temperature of >50° C. The solution was then cooled slowly to 10° C. during which time crystallization occurred. The mixture was stirred for an additional 30 minutes and filtered through a medium glass fritted funnel and the filter cake washed with cold hexanes (330 mL). The material was dried to constant weight in a vacuum oven at 40° C. to yield 183.1 g (76%) of 8 as a cream solid; mp 127-129° C.; 1HNMR (400 MHz, DMSO-d6): δ 0.80 (t, J=7.3 Hz, 3H), 1.69 (h, J=7.2 Hz, 1H), 2.04 (h, J=7.2 Hz, 1H), 4.62 (t, J=7.2 Hz, 1H), 6.79 (d, J=8.7 Hz, 2H), 7.15-7.33 (m, 5H), 7.91 (d, J=8.7 Hz, 2H), 10.32 (s, 1H). until dissolved did not rise above 15° C The solution was heated to 35° C. for 1 h The solution was cooled to 20° C. with external cooling vigorous stirring at a rate such that the reaction temperature did not rise above 35° C The mixture was stirred for 1 h The aqueous layer was removed the upper organic layer was washed with H2O (900 mL) The aqueous layer was removed the toluene layer concentrated to ˜1000 mL via atmospheric distillation The solution was stirred at 70° C. for 1 h cooled to 15° C. with cooling such that the temperature did not exceed 40° C After complete addition cooling to 25° C. stirred for 5 minutes The lower aqueous layer was removed the organic layer washed with water (1000 mL) The organic layer was concentrated under reduced pressure (˜60° C.) to ˜1000 mL The solution was then cooled to 50° C. hexanes (660 mL) added while maintaining an internal temperature of >50° C The solution was then cooled slowly to 10° C. during which time crystallization The mixture was stirred for an additional 30 minutes filtered through a medium glass fritted funnel the filter cake washed with cold hexanes (330 mL) The material was dried to constant weight in a vacuum oven at 40° C.

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

Procedure: A mixture of 4-hydroxy-α-ethyldesoxybenzoin (44.5 g.), sodium carbonate (18.5 g.), potassium iodide (1.4 g.) and benzyl chloride (19 ml.) in ethanol (350 ml.) and water (50 ml.) was stirred and heated under reflux for 8 hours. The mixture was cooled, filtered and the residue washed with water to give 4-benzyloxy-α-ethyldesoxybenzoin (54.3 g.), m.p. 71° C. heated under reflux for 8 hours The mixture was cooled filtered the residue washed with water

Conditions: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.4 G. (0.10 mole) 1-(4'-methoxyphenyl)-2-phenyl-n-butan-1-one and 34.5 g. (0.30 mole) pyridine hydrochloride are melted and refluxed at 220° C. for one hour while being agitated. The melt while still liquid is poured into ice water and the precipitate dissolved in 400 ml. ether. After washing the etheric solution with water, it is shaken out with 1 N sodium hydroxide solution. The aqueous alkaline solution is acidified with 5 N hydrochlc.ric acid and extracted with 500 ml. ether. The organic phase is washed with water and dried over sodium sulfate. The solvent is removed in vacuo and the crude product is crystallized from dilute ethanol. Obtained are colorless crystals having a melting point of 131° C.; Rf 0.45 [toluene/ethyl acetate (9/1)]; yield: 16.3 g. (68%). the precipitate dissolved in 400 ml After washing the etheric solution with water, it is shaken out with 1 N sodium hydroxide solution extracted with 500 ml The organic phase is washed with water dried over sodium sulfate The solvent is removed in vacuo the crude product is crystallized from dilute ethanol Obtained

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

Procedure: 4-(β-Dimethylaminoethoxy)-α-ethyldesoxybenzoin (b.p. 162° C./0.075 mm.) may be obtained from α-ethyl-4-hydroxydesoxybenzoin by an analogous procedure to that described below for the preparation of 4-(β-dimethylaminoethoxy)-α-methyldesoxybenzoin, and α-ethyl-4-hydroxydesoxybenzoin itself (m.p. 122°-124° C.) may be obtained from α-ethyl-4-methoxydesoxybenzoin by an analogous procedure to that described below for the preparation of 4-hydroxy-α-methyldesoxybenzoin.