octan-3-one

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Quantification shows that 606.3 g 6-methylheptanone (4.73 mole) were obtained, which corresponds to a 95.4% yield of methylheptanone in relation to isovaleral. The isovaleraldehyde conversion is 99.2%. were obtained

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

実験手順: To a well-stirred solution of 19.2 g (0.15 mmol) of 3-octanone in 270 ml of 95% ethanol, cooled in an ice bath, was added in portions a solution of 3.9 g (0.103 mmol) of sodium borohydride in 27 ml of water. Ammonium hydroxide (15M, 27 ml) was added and the ice bath removed and stirring was continued in room temperature for 3 hr. The reaction mixture was concentrated to near dryness and the residue was partitioned between 250 ml each of CHCl3 and H2O. The organic layer was separated and the aqueous layer was extracted with CHCl3 (2×200 ml). The combined extracts were washed with 5% HCl (350 ml), and saturated NaCl solution (350 ml) and dried over MgSO4. After the removal of the solvent, the liquid residue was distilled under reduced pressure (bp 86°-87° C./24 Torr; lit. bp 69.5°-70.4° C./7 Torr (18)) to give 15.41 g (79.02%) of pure 3-octanol. NMR(CDCl3): δ0.93 (6H, t, CH3), δ1.37 (10H, broad multiplet, --CH2 --), δ2.35 (1H, broad singlet, exchangeable with D2O and shift to low field in pyridine, --OH), δ3.47 (1H, m, >CHO--). the ice bath removed The reaction mixture was concentrated the residue was partitioned between 250 ml each of CHCl3 and H2O The organic layer was separated the aqueous layer was extracted with CHCl3 (2×200 ml) The combined extracts were washed with 5% HCl (350 ml), and saturated NaCl solution (350 ml) dried over MgSO4 After the removal of the solvent the liquid residue was distilled under reduced pressure (bp 86°-87° C./24 Torr; lit. bp 69.5°-70.4° C./7 Torr (18))

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

実験手順: In a manner similar to Preparation 8, react 2-[4-(1H-imidazol-1-yl)phenoxy]ethanamine with 3-octanone and sodium cyanoborohydride in methanol to obtain the title compound. In a manner similar to Preparation 8

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

実験手順: Anionic polymerization was also done. This was carried out in tetrahydrofuran at 0° C. by using benzophenone monothithium complex as an initiator. After a specified time, a sufficient amount of acetic anhydride was added to the solution and the resulting mixture was stirred at room temperature for several hours. The separation and purification of the polymer were similar to those described for the cationic polymerization. IR (film) 1738 (νC=O), 1125 (νC-O-C) cm-1 ; 1H NMR (CDCl3) δ6.12 (H-2eq), 5.95 (H-2ax), 3.8 4.2 (2H-6), 2.5-2.8 (H-5), 1.6 2.2 (2H-3, 2H-4); Anal. Calcd. for (C6H8O3)n ; C 56, H 6.29. Found; C 56.28 H 6.11. Anionic polymerization The separation and purification of the polymer those described for the cationic polymerization

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

実験手順: A solution of the product obtained in Example IV (2.7 g, 0.017 mol) and p-toluenesulfonic acid monohydrate (0.023) g, 0.12 mmol) in dry toluene (200 ml) was allowed to reflux through a Soxhlet extractor for 2 hours. The Soxhlet thimble was charged with Type 4 A molecular sieves (16 g). After the solution was cooled to room temperature, anhydrous potassium carbonate (5 g, 0.036 mol) was added to the solution, and the mixture was stirred at room temperature for 30 min. The mixture was filtered and subjected to rotary evaporation to afford a slightly yellow wax at a 68% yield. Recrystallization from ethyl ether gave white crystals having a melting point of 69° C. to reflux through a Soxhlet extractor for 2 hours The Soxhlet thimble was charged with Type 4 A molecular sieves (16 g) The mixture was filtered subjected to rotary evaporation to afford a slightly yellow wax at a 68% yield Recrystallization from ethyl ether gave white crystals

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

実験手順: To a solution of 6(7)-hydroxy-2-methoxycarbonyl-8-azabicyclo(3.2.1)octane-3-one (18 g, 84.5 mmol) in 200 ml of CH2Cl2, 70 ml of dimethoxymethane was added, followed by (18 g, 93 mmol) of p-toluene sulfonic acid monohydrate. The round-bottom flask was fitted with a soxhiet extractor containing 3-4 A molecular sieves. The reaction mixture was heated to reflux with stirring until the starting material had disappeared (TLC). The mixture was cooled and treated with sat. sodium bicarbonate solution and extracted with CH2Cl2. The combined organics were dried over K2CO3 removed in vacuo and applied to column (silica gel, 10% Et3N, 30% EtOAc/hexane). 6-Methoxymethoxy-2-methoxy-carbonyl-8-azabicyclo(3.2.1))octane-3-one (2.2 g) was obtained as a yellow oil. Rf 0.3 (10% Et3N, 30% EtOAc in hexane). The round-bottom flask was fitted with a soxhiet extractor containing 3-4 A molecular sieves The reaction mixture was heated to reflux The mixture was cooled extracted with CH2Cl2 The combined organics were dried over K2CO3 removed in vacuo

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

実験手順: To a solution of 6(7)-hydroxy-2-methoxycarbonyl-8-azabicyclo(3.2.1)octane-3-one (18 g, 84.5 mmol) in 200 ml of CH2Cl2, 70 ml of dimethoxymethane was added, followed by (18 g, 93 mmol) of p-toluene sulfonic acid monohydrate. The round-bottom flask was fitted with a soxhiet extractor containing 3-4 A molecular sieves. The reaction mixture was heated to reflux with stirring until the starting material had disappeared (TLC). The mixture was cooled and treated with sat. sodium bicarbonate solution and extracted with CH2Cl2. The combined organics were dried over K2CO3 removed in vacuo and applied to column (silica gel, 10% Et3N, 30% EtOAc/hexane). 6-Methoxymethoxy-2-methoxy-carbonyl-8-azabicyclo(3.2.1))octane-3-one (2.2 g) was obtained as a yellow oil. Rf 0.3 (10% Et3N, 30% EtOAc in hexane). The round-bottom flask was fitted with a soxhiet extractor containing 3-4 A molecular sieves The reaction mixture was heated to reflux The mixture was cooled extracted with CH2Cl2 The combined organics were dried over K2CO3 removed in vacuo

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

実験手順: Quantification shows that 606.3 g 6-methylheptanone (4.73 mole) were obtained, which corresponds to a 95.4% yield of methylheptanone in relation to isovaleral. The isovaleraldehyde conversion is 99.2%. were obtained

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

実験手順: To a well-stirred solution of 19.2 g (0.15 mmol) of 3-octanone in 270 ml of 95% ethanol, cooled in an ice bath, was added in portions a solution of 3.9 g (0.103 mmol) of sodium borohydride in 27 ml of water. Ammonium hydroxide (15M, 27 ml) was added and the ice bath removed and stirring was continued in room temperature for 3 hr. The reaction mixture was concentrated to near dryness and the residue was partitioned between 250 ml each of CHCl3 and H2O. The organic layer was separated and the aqueous layer was extracted with CHCl3 (2×200 ml). The combined extracts were washed with 5% HCl (350 ml), and saturated NaCl solution (350 ml) and dried over MgSO4. After the removal of the solvent, the liquid residue was distilled under reduced pressure (bp 86°-87° C./24 Torr; lit. bp 69.5°-70.4° C./7 Torr (18)) to give 15.41 g (79.02%) of pure 3-octanol. NMR(CDCl3): δ0.93 (6H, t, CH3), δ1.37 (10H, broad multiplet, --CH2 --), δ2.35 (1H, broad singlet, exchangeable with D2O and shift to low field in pyridine, --OH), δ3.47 (1H, m, >CHO--). the ice bath removed The reaction mixture was concentrated the residue was partitioned between 250 ml each of CHCl3 and H2O The organic layer was separated the aqueous layer was extracted with CHCl3 (2×200 ml) The combined extracts were washed with 5% HCl (350 ml), and saturated NaCl solution (350 ml) dried over MgSO4 After the removal of the solvent the liquid residue was distilled under reduced pressure (bp 86°-87° C./24 Torr; lit. bp 69.5°-70.4° C./7 Torr (18))

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

実験手順: In a manner similar to Preparation 8, react 2-[4-(1H-imidazol-1-yl)phenoxy]ethanamine with 3-octanone and sodium cyanoborohydride in methanol to obtain the title compound. In a manner similar to Preparation 8

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

実験手順: The molar ratio of the 2-ethyl hexanal to the formaldehyde, used as the initial materials of the reaction, should be within the range 1:2 to 1:4, preferably within the range 1:2.5 to 1:3.5. To the mixture is added a neutral or cationic phase transfer catalyst, such as neutral polyethylene glycol (e.g. PEG 400) or a cationic tetrabutylammoniumhydrogen sulfate (TBAHSO4) or tricaprylmethylammonium chloride (Aliquat 336). These are added in an amount of 1-50% by weight, preferably 5-30% by weight, of the mass of the formalin solution or, if solid paraformaldehyde is used, in an amount of 1-20% by weight, preferably 3-10% by weight, of the mass of the aqueous solution and solid paraformaidehyde, or in an amount of 1-50% by weight, preferably 5-15% by weight, of the amount of 2-ethyl hexanal. The mixture of the initial materials is heated to 30°-100° C., preferably to 50°-80° C., and most preferably to 60°-80° C., and an aqueous solution of the alkali metal hydroxide or earth alkali metal hydroxide is added to the mixture, drop by drop, in the course of up to 5 h, preferably 1-3 h, and the reaction is continued at the said temperature for up to 3 h, preferably 15 min-2 h, most preferably 15 min-1 h 15 min. The alkali metal hydroxide or earth alkali metal hydroxide is used in a molar amount 1:1 to 2:1, preferably in a molar amount of 1.25:1 to 1.75:1 to that of 2:1-ethyl hexanal. After this reaction step the mixture is neutralized with an organic acid or a mineral acid, preferably for example sulfuric acid, and the phases are separated from each other, preferably while they are hot. The organic phase is washed with water once or several times, preferably 1-2 times, by using for the wash an amount of water at minimum 50% of the mass of the organic phase. The phases are separated and the organic phases are combined and vacuum distilled. The boiling point of the final product is 130°-132° C./9 mmHg. The yield obtained for 2-n-butyl-2-ethyl-1,3-propane diol was up to more than 92%, depending on the reaction conditions and the molar proportions. To the mixture is added a neutral or cationic phase transfer catalyst is heated to 30°-100° C., preferably to 50°-80° C. preferably 1-3 h up to 3 h preferably 15 min-2 h, most preferably 15 min-1 h 15 min After this reaction step the mixture The organic phase is washed with water once wash an amount of water at minimum 50% of the mass of the organic phase The phases are separated vacuum distilled is 130°-132° C.