2-methylcyclohexane-1,3-dione

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:

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

Procedure: A modification of the procedure of Ijima et al. Chem. Pharm. Bull. 19, 1053-5 (1971) was used. A solution of 2-methyl-1,3-cyclohexanedione (40 g, 0.317 mole, Aldrich) and Ba(OH)2.8H2O (360 g) in water (840 mL) was heated at reflux for 48 h. After standing overnight at room temperature and cooling to 0° C., the precipitated barium hydroxide was removed by suction filtration. CO2 gas (generated from Dry Ice) was bubbled through the filtrate to precipitate any remaining barium hydroxide as barium carbonate. The precipitate was removed by suction filtration, and water was removed in vacuum until crystallization started. The resulting mixture was acidified to pH 1 (conc. HCl) and extracted with OEt2 (3×300 mL). The extract was dried (Na2SO4) and stripped of solvent in vacuum giving 5-oxoheptanoic acid (Compound XXI) as a white solid (43.3-45.1 g, 95-99%, lit.112 69%): mp 48°-49.5° C. (lit.182 50° C.); IR (KBr pellet) cm-1 3000 (very br), 1725, 1710, 1690, 1460, 1435, 1420, 1380, 1340, 1280, 1210, 1120, 1085, 985, 910, 770, 685; 1H NMR (200 MHz, CDCl3) δ 10.2 (br, 1H), 2.51 (t, 7.1 Hz, 2H), 2.43 (q, 7.3 Hz, 2H), 2.40 (t, 7.1 Hz, 2H), 1.91 (rough pentet, 2H), 1.06 (t, 7.3 Hz, 3H); 13C NMR (22.5 MHz, CDCl3) δ 211.5, 178.6, 41.0, 36.0, 33.1, 18.7, 7.8; mass spectrum (16 eV) m/e (% base) 144 (M+, 4.1), 126 (61.3), 115 (88.8), 98 (40.0), 87 (40.1), 70 (21.3), 57 (100); TLC (OEt2, I2) Rf=0.37. at reflux for 48 h the precipitated barium hydroxide was removed by suction filtration CO2 gas (generated from Dry Ice) was bubbled through the filtrate to precipitate any remaining barium hydroxide as barium carbonate The precipitate was removed by suction filtration, and water was removed in vacuum until crystallization extracted with OEt2 (3×300 mL) The extract was dried (Na2SO4)

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

Procedure: A modification of the procedure of Ijima et al. Chem. Pharm. Bull. 19, 1053-5 (1971) was used. A solution of 2-methyl-1,3-cyclohexanedione (40 g, 0.317 mole, Aldrich) and Ba(OH)2.8H2O (360 g) in water (840 mL) was heated at reflux for 48 h. After standing overnight at room temperature and cooling to 0° C., the precipitated barium hydroxide was removed by suction filtration. CO2 gas (generated from Dry Ice) was bubbled through the filtrate to precipitate any remaining barium hydroxide as barium carbonate. The precipitate was removed by suction filtration, and water was removed in vacuum until crystallization started. The resulting mixture was acidified to pH 1 (conc. HCl) and extracted with OEt2 (3×300 mL). The extract was dried (Na2SO4) and stripped of solvent in vacuum giving 5-oxoheptanoic acid (Compound XXI) as a white solid (43.3-45.1 g, 95-99%, lit.112 69%): mp 48°-49.5° C. (lit.182 50° C.); IR (KBr pellet) cm-1 3000 (very br), 1725, 1710, 1690, 1460, 1435, 1420, 1380, 1340, 1280, 1210, 1120, 1085, 985, 910, 770, 685; 1H NMR (200 MHz, CDCl3) δ 10.2 (br, 1H), 2.51 (t, 7.1 Hz, 2H), 2.43 (q, 7.3 Hz, 2H), 2.40 (t, 7.1 Hz, 2H), 1.91 (rough pentet, 2H), 1.06 (t, 7.3 Hz, 3H); 13C NMR (22.5 MHz, CDCl3) δ 211.5, 178.6, 41.0, 36.0, 33.1, 18.7, 7.8; mass spectrum (16 eV) m/e (% base) 144 (M+, 4.1), 126 (61.3), 115 (88.8), 98 (40.0), 87 (40.1), 70 (21.3), 57 (100); TLC (OEt2, I2) Rf=0.37. at reflux for 48 h the precipitated barium hydroxide was removed by suction filtration CO2 gas (generated from Dry Ice) was bubbled through the filtrate to precipitate any remaining barium hydroxide as barium carbonate The precipitate was removed by suction filtration, and water was removed in vacuum until crystallization extracted with OEt2 (3×300 mL) The extract was dried (Na2SO4)

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

Procedure: 1-Bromo-5-methoxyheptane (Compound XX) is a reagent used for preparing preferred compounds X and XX. Compound XX is prepared in accordance with Reaction Scheme 3, starting from commercially available 2-methyl-1,3-cyclohexanedione. Thus, with reference to Reaction Scheme 3, 2-methyl-1,3-cyclohexanedione is reacted with base (Ba(OH)2) to yield 5-oxoheptanoic acid (Compound XXI). The oxo function of 5-oxoheptanoic acid (Compound XXI) is thereafter reduced, and the resulting hydroxy group, as well as the carboxylate function, are methylated to give methyl 5-methoxyheptanoate (Compound XXII). The carboxylate group of the latter is reduced (LiAlH4) to give 5-methoxy-1-heptanol (Compound XXIII), which is thereafter reacted with carbontetrabromide to yield 1-bromo-5-methoxyheptane (compound XX). ##STR6## used for preparing

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

Procedure: 1-Bromo-5-methoxyheptane (Compound XX) is a reagent used for preparing preferred compounds X and XX. Compound XX is prepared in accordance with Reaction Scheme 3, starting from commercially available 2-methyl-1,3-cyclohexanedione. Thus, with reference to Reaction Scheme 3, 2-methyl-1,3-cyclohexanedione is reacted with base (Ba(OH)2) to yield 5-oxoheptanoic acid (Compound XXI). The oxo function of 5-oxoheptanoic acid (Compound XXI) is thereafter reduced, and the resulting hydroxy group, as well as the carboxylate function, are methylated to give methyl 5-methoxyheptanoate (Compound XXII). The carboxylate group of the latter is reduced (LiAlH4) to give 5-methoxy-1-heptanol (Compound XXIII), which is thereafter reacted with carbontetrabromide to yield 1-bromo-5-methoxyheptane (compound XX). ##STR6## used for preparing

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

Procedure: Add to the crude undistilled ketoamine 1-diethylamino-6-(m-methoxyphenyl)hexan-3-one (2.3 g), the material obtained by hydration of the acetylenic amine, 2-methylcyclohexane-1,3-dione (1 g), pyridine (1 cc) and benzene (12 cc), and reflux the mixture for 15 hours. Cool the mixture and filter off unreacted dione, add a little ether to the filtrate, and wash the ethereal solution with acid, and then water, and dry. Evaporate the solvents to obtain as residue crude 2-(6-m-methoxyphenyl-3-oxohexyl)-2-methylcyclohexane-1,3-dione (1.7 g).

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

Procedure: To a suspension of p-chlorophenylhydrazine hydrochloride (8.52 g) in toluene (100 ml) were added 2-methylcyclohexane-1,3-dione (5.0 g) and 40% sulfuric acid (40 ml), and the mixture was stirred at 80°-85° C. for 4 hours. After cooling, the organic layer was separated. The aqueous layer was extracted with toluene. The organic layers were combined and washed with aqueous sodium bicarbonate, water, and brine. After dried over sodium sulfate, the organic layer was evaporated. The residue was recrystallized from methanol to give 2-chloro-8,9-dihydro-10-methylpyrido[1,2-a]indol-6(7H)-one (4.63 g). After cooling the organic layer was separated The aqueous layer was extracted with toluene washed with aqueous sodium bicarbonate, water, and brine After dried over sodium sulfate the organic layer was evaporated The residue was recrystallized from methanol

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

Procedure: To a suspension of p-chlorophenylhydrazine hydrochloride (8.52 g) in toluene (100 ml) were added 2-methylcyclohexane-1,3-dione (5.0 g) and 40% sulfuric acid (40 ml), and the mixture was stirred at 80°-85° C. for 4 hours. After cooling, the organic layer was separated. The aqueous layer was extracted with toluene. The organic layers were combined and washed with aqueous sodium bicarbonate, water, and brine. After dried over sodium sulfate, the organic layer was evaporated. The residue was recrystallized from methanol to give 2-chloro-8,9-dihydro-10-methylpyrido[1,2-a]indol-6(7H)-one (4.63 g). After cooling the organic layer was separated The aqueous layer was extracted with toluene washed with aqueous sodium bicarbonate, water, and brine After dried over sodium sulfate the organic layer was evaporated The residue was recrystallized from methanol

Conditions: temp:82.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of p-chlorophenylhydrazine hydrochloride (8.52 g) in toluene (100 ml) were added 2-methylcyclohexane-1,3-dione (5.0 g) and 40% sulfuric acid (40 ml), and the mixture was stirred at 80-85° C. for 4 hours. After cooling, the organic layer was separated. The aqueous layer was extracted with toluene. The organic layers were combined and washed with aqueous sodium bicarbonate, water, and brine. After dried over sodium sulfate, the organic layer was evaporated. The residue was recrystallized from methanol to give 2-chloro-8,9-dihydro-10-methylpyrido[1,2-a]indol-6(7H)-one (4.63 g). After cooling the organic layer was separated The aqueous layer was extracted with toluene washed with aqueous sodium bicarbonate, water, and brine After dried over sodium sulfate the organic layer was evaporated The residue was recrystallized from methanol