3-(3-methoxyphenyl)propan-1-ol

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

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

Procedure: Allyl bromide (25 mL, 0.28 mmol) was added to a solution of 3-(3-methoxyphenyl)propanol (8.8 g, 0.053 mol), N,N′-carbonyldiimidazole (9.6 g, 0.0605 mol) and CH3CN (45 mL) at room temperature. After 1.5 hr at rt and 1.5 hr at reflux, the reaction mixture was cooled, partitioned between EtOAc (250 mL) and H2O (300 mL), the organic layer washed with H2O (300mL), 5% HCl (200 mL), dilute NaHCO3 solution (200 mL), brine (300 mL), and dried (Na2SO4). Filtration and concentration to dryness gave the title compound. 1.5 hr at reflux the reaction mixture was cooled partitioned between EtOAc (250 mL) and H2O (300 mL) the organic layer washed with H2O (300mL), 5% HCl (200 mL), dilute NaHCO3 solution (200 mL), brine (300 mL) dried (Na2SO4) Filtration and concentration to dryness

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(3-Methoxyphenyl)propionic acid (see Example 1, Step J) (10.09 g, 0.058 mol) dissolved in anhydrous THF 60 mL) was added dropwise to a solution of LiAlH4 (1M in THF) (60 mL, 0.06 mol) in THF (60 mL) at ambient temperature under Ar. The resulting solution was stirred at reflux for 6 hr, then cooled to 0° C., treated dropwise with H2O (2.2 mL), 20% NaOH (1.7 mL), then H2O (6.62 mL). After stirring for 15 min, MgSO4 was added, stirring was continued for 15 min, the solids were filtered off, washed well with EtOAc, and the filtrate concentrated to dryness to give the title compound. MS (M+1) 167.1 at reflux for 6 hr After stirring for 15 min stirring the solids were filtered off washed well with EtOAc the filtrate concentrated to dryness

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

Procedure: Compound 16-1 (2.00 g) was dissolved in methylene chloride (50 ml), triphenylphosphine (3.58 g) and N-bromosuccinimide (2.40 g) were added under ice-cooling, and the mixture was stirred under ice-cooling for 1 hr, and further at room temperature for 15 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Diethyl ether (100 ml) was added, and the precipitated triphenylphosphine oxide was filtered off. The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone) to give the object product (2.07 g) as a pale-yellow oil. cooling cooling for 1 hr The reaction mixture was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure Diethyl ether (100 ml) was added the precipitated triphenylphosphine oxide was filtered off The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone)

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

Procedure: Referring now to FIG. 1, wherein the compounds are assigned Roman numerals for identification schematically, the sequence of reactions involved in the synthesis of a specific embodiment, namely, 13β,17α-diethyl-17β-hydroxygon-4-en-3-one, is illustrated. 3-(m-Methoxyphenyl)propanol (I) is heated with phosphorus tribromide in benzene after dropwise addition in the cold to form 3-(m-methoxyphenyl)propyl bromide (II). This halogen compound (II) dissolved in tetrahydrofuran is condensed with sodium acetylide in liquid ammonia to obtain 5-(m-methoxyphenyl)-1-pentyne (III). Compound III is allowed to stand under nitrogen with water, 30% formalin, acetic acid, diethylamine, dioxan, and cuprous chloride a 70°C for about 12 hours, whereby there is obtained 1-diethylamino-6-(m-methoxyphenyl)-2-hexyne (IV), which is in turn hydrated in the presence of a mercury salt and sulfuric acid to form 1-diethylamino-6-(m-methoxyphenyl)-3-hexanone (V). The ketamine (V) may eliminate diethylamine on distillation to give the vinyl ketone 6-m-methoxyphenyl)-1-hexen-3-one (VI). Either the ketamine (V) or the ketone (VI), or mixtures thereof, is then reacted with 2-ethyl-1,3-cyclopentanedione (VII) under Michael condensation conditions, e.g. refluxing in methanolic potassium hydroxide to form 2-ethyl-2-[6-(m-methoxyphenyl)-3-oxohexyl]-1,3-cyclopentanedione (VIII). the sequence of reactions involved in the synthesis of a specific embodiment after dropwise addition in the cold

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

Procedure: Referring now to FIG. 1, wherein the compounds are assigned Roman numerals for identification schematically, the sequence of reactions involved in the synthesis of a specific embodiment, namely, 13β,17α-diethyl-17β-hydroxygon-4-en-3-one, is illustrated. 3-(m-Methoxyphenyl)propanol (I) is heated with phosphorus tribromide in benzene after dropwise addition in the cold to form 3-(m-methoxyphenyl)propyl bromide (II). This halogen compound (II) dissolved in tetrahydrofuran is condensed with sodium acetylide in liquid ammonia to obtain 5-(m-methoxyphenyl)-1-pentyne (III). Compound III is allowed to stand under nitrogen with water, 30% formalin, acetic acid, diethylamine, dioxan, and cuprous chloride a 70°C for about 12 hours, whereby there is obtained 1-diethylamino-6-(m-methoxyphenyl)-2-hexyne (IV), which is in turn hydrated in the presence of a mercury salt and sulfuric acid to form 1-diethylamino-6-(m-methoxyphenyl)-3-hexanone (V). The ketamine (V) may eliminate diethylamine on distillation to give the vinyl ketone 6-m-methoxyphenyl)-1-hexen-3-one (VI). Either the ketamine (V) or the ketone (VI), or mixtures thereof, is then reacted with 2-ethyl-1,3-cyclopentanedione (VII) under Michael condensation conditions, e.g. refluxing in methanolic potassium hydroxide to form 2-ethyl-2-[6-(m-methoxyphenyl)-3-oxohexyl]-1,3-cyclopentanedione (VIII). the sequence of reactions involved in the synthesis of a specific embodiment after dropwise addition in the cold

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

Procedure: Allyl bromide (25 mL, 0.28 mmol) was added to a solution of 3-(3-methoxyphenyl)propanol (8.8 g, 0.053 mol), N,N′-carbonyldiimidazole (9.6 g, 0.0605 mol) and CH3CN (45 mL) at room temperature. After 1.5 hr at rt and 1.5 hr at reflux, the reaction mixture was cooled, partitioned between EtOAc (250 mL) and H2O (300 mL), the organic layer washed with H2O (300mL), 5% HCl (200 mL), dilute NaHCO3 solution (200 mL), brine (300 mL), and dried (Na2SO4). Filtration and concentration to dryness gave the title compound. 1.5 hr at reflux the reaction mixture was cooled partitioned between EtOAc (250 mL) and H2O (300 mL) the organic layer washed with H2O (300mL), 5% HCl (200 mL), dilute NaHCO3 solution (200 mL), brine (300 mL) dried (Na2SO4) Filtration and concentration to dryness

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(3-Methoxyphenyl)propionic acid (see Example 1, Step J) (10.09 g, 0.058 mol) dissolved in anhydrous THF 60 mL) was added dropwise to a solution of LiAlH4 (1M in THF) (60 mL, 0.06 mol) in THF (60 mL) at ambient temperature under Ar. The resulting solution was stirred at reflux for 6 hr, then cooled to 0° C., treated dropwise with H2O (2.2 mL), 20% NaOH (1.7 mL), then H2O (6.62 mL). After stirring for 15 min, MgSO4 was added, stirring was continued for 15 min, the solids were filtered off, washed well with EtOAc, and the filtrate concentrated to dryness to give the title compound. MS (M+1) 167.1 at reflux for 6 hr After stirring for 15 min stirring the solids were filtered off washed well with EtOAc the filtrate concentrated to dryness

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(3-Methoxyphenyl)propionic acid (see Example 1, Step J) (10.09 g, 0.058 mol) dissolved in anhydrous THF 60 mL) was added dropwise to a solution of LiAlH4 (1M in THF) (60 mL, 0.06 mol) in THF (60 mL) at ambient temperature under Ar. The resulting solution was stirred at reflux for 6 hr, then cooled to 0° C., treated dropwise with H2O (2.2 mL), 20% NaOH (1.7 mL), then H2O (6.62 mL). After stirring for 15 min, MgSO4 was added, stirring was continued for 15 min, the solids were filtered off, washed well with EtOAc, and the filtrate concentrated to dryness to give the title compound. MS (M+1) 167.1 at reflux for 6 hr After stirring for 15 min stirring the solids were filtered off washed well with EtOAc the filtrate concentrated to dryness

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

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

Procedure: A solution of 3-(3-methoxyphenyl)-propanol (69 g, 0.42 mole) and pyridine (400 mL) was stirred at 5° C. as p-toluenesulfonyl chloride (87 g, 0.46 mole) was added portionwise. The reaction mixture was stirred at room temperature for 2 hours, then was poured onto ice/concentrated HCl and was extracted with ether. The extracts were washed with 2N HCl, wawter, saturated aqueous NaCl, dried (MgSO4), filtered, and evaporated to yield 126 g yellow oil, (95%); M+ 320. was added portionwise was poured onto ice/concentrated HCl was extracted with ether The extracts were washed with 2N HCl, wawter, saturated aqueous NaCl dried (MgSO4) filtered evaporated

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

Procedure: A solution of dihydro-m-methoxycinnamic acid (90 g, 0.5 mole) and tetrahydrofuran (250 mL) was stirred under N2 at 0° as BH3.THF (1M solution, 525 mL) was added slowly. The reaction mixture was stirred at room temperature for 2 hours. After cooling to -5° C., 1N HCl was added. THF was evaporated and water was added to the residue. The aqueous layer was extracted with ether. The combined extracts were washed with saturated aqueous NaHCO3, saturated aqueous NaCl, dried (MgSO4), filtered and evaporated to yield 70.0 g white solid, M+ 166. was added slowly After cooling to -5° C. THF was evaporated water was added to the residue The aqueous layer was extracted with ether The combined extracts were washed with saturated aqueous NaHCO3, saturated aqueous NaCl dried (MgSO4) filtered evaporated