5-oxoheptanoic acid

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Fraction (b) contains 95% by weight of ethyl ester of 3-methyl-4-oxopentane-1-carboxylic acid and 2% by weight of ethyl ester of 4-oxo-hexane-1-carboxylic acid. 41% of the total amount of ethyl acrylate has been converted. The efficiency in ethyl ester of 3-methyl-4-oxo-pentane-1-carboxylic acid amounts to 56% referred to the quantity of converted methyl ethyl ketone, and to 58% referred to the quantity of converted ethyl acrylate.

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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