methyl 3-oxohexanoate

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

Procedure: To a solution of 2.88 g (20 mmol) of methyl 3-ketohexanoate in 10 ml methanol, 36 mg (0.004 mmol) RuCl2(R)-binap was added and stirred in an autoclave under a hydrogen pressure of 100 atm at 30° C. for 66 hours. After concentration and distillation, 2.24 g (15.4 mmol, 99% ee) of methyl (S)-3-hydroxyhexanoate was obtained. The condition of chiral HPLC is the following. Column, CHIRALPAK OD-H manufactured by Daicel Chemical Industries, Ltd.; Eluate, Hexane:2-propanol=90:10; flow rate, 1.0 mL/min; Wavelength of detection, 210 nm; Temperature, 25° C.; Retention time, 5 min (R) and 7 min (S). After concentration and distillation

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

Procedure: Process 1: Under argon atmosphere, tetrahydrofuran (20 mL) mixture containing 2-[5-(bromomethyl)pyridin-2-yl]benzonitrile (1.1 g, 3.9 mmol), methyl 3-oxohexanoate (0.68 g, 4.7 mmol), diisopropylethylamine (1.0 g, 7.8 mmol), and lithium bromide monohydrate (0.49 g, 4.7 mmol) was refluxed under heating for 18 hours. The reaction mixture was added water and extracted three times with chloroform. The organic layer was combined, washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residues were subjected to silica gel column chromatography (SNAP100HP manufactured by Biotage) (hexane/ethyl acetate; 5/1→1/1) to give methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxohexanoate (1.2 g, 91%) as yellow oil. was refluxed under heating for 18 hours extracted three times with chloroform washed with water and brine dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: Process 1: Under argon atmosphere, tetrahydrofuran (20 mL) mixture containing 2-[5-(bromomethyl)pyridin-2-yl]benzonitrile (1.1 g, 3.9 mmol), methyl 3-oxohexanoate (0.68 g, 4.7 mmol), diisopropylethylamine (1.0 g, 7.8 mmol), and lithium bromide monohydrate (0.49 g, 4.7 mmol) was refluxed under heating for 18 hours. The reaction mixture was added water and extracted three times with chloroform. The organic layer was combined, washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residues were subjected to silica gel column chromatography (SNAP100HP manufactured by Biotage) (hexane/ethyl acetate; 5/1→1/1) to give methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxohexanoate (1.2 g, 91%) as yellow oil. was refluxed under heating for 18 hours extracted three times with chloroform washed with water and brine dried over anhydrous sodium sulfate concentrated in vacuo

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

Procedure: The title compound was prepared from 2-chlorobenzaldehyde, 3-aminopyrazole and methyl 3-ketohexanoate in the same manner as in Example 25.

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

Procedure: Under a nitrogen atmosphere, a solution of bromine (8.61 mL, 167 mmol) in chloroform (20 mL) was added drop-wise over a period of 2 h to a solution of methyl 3-oxohexanoate (Fluka, 24.1 g, 167 mmol) in chloroform (147 mL), at 0° C. (ice bath). The reaction mixture was stirred for 30 min at 0° C. and then allowed to warm to room temperature overnight. While stirring, a stream of air was bubbled through the solution for 1 hour. The reaction mixture was dried over sodium sulfate and the solvent evaporated under reduced pressure to provide the desired compound. at 0° C. to warm to room temperature overnight While stirring a stream of air was bubbled through the solution for 1 hour The reaction mixture was dried over sodium sulfate the solvent evaporated under reduced pressure

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

Procedure: Under a nitrogen atmosphere, a solution of bromine (8.61 mL, 167 mmol) in chloroform (20 mL) was added drop-wise over a period of 2 h to a solution of methyl 3-oxohexanoate (Fluka, 24.1 g, 167 mmol) in chloroform (147 mL), at 0° C. (ice bath). The reaction mixture was stirred for 30 min at 0° C. and then allowed to warm to room temperature overnight. While stirring, a stream of air was bubbled through the solution for 1 hour. The reaction mixture was dried over sodium sulfate and the solvent evaporated under reduced pressure to provide the desired compound. at 0° C. to warm to room temperature overnight While stirring a stream of air was bubbled through the solution for 1 hour The reaction mixture was dried over sodium sulfate the solvent evaporated under reduced pressure

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

Procedure: Methyl 3-ketohexanoate (44.7 g, 310 mmol) was diluted with methanol (75 mL) and 0.2N HCl (2 mL). Et2NH2 +Ru2Cl5- (BINAP)2 (200 mg) was added and the mixture was heated at 60° under 100 psi of hydrogen for 2 hours. Toluene (100 mL) was added and the mixture was concentrated to an oil weighing 75 g. the mixture was concentrated to an oil

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

Procedure: Methyl 3-ketohexanoate (44.7 g, 310 mmol) was diluted with methanol (75 mL) and 0.2N HCl (2 mL). Et2NH2 +Ru2Cl5- (BINAP)2 (200 mg) was added and the mixture was heated at 60° under 100 psi of hydrogen for 2 hours. Toluene (100 mL) was added and the mixture was concentrated to an oil weighing 75 g. the mixture was concentrated to an oil

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

Procedure: Methyl 3-ketohexanoate (44.7 g, 310 mmol) was diluted with methanol (75 mL) and 0.2N HCl (2 mL). Et2NH2 +Ru2Cl5- (BINAP)2 (200 mg) was added and the mixture was heated at 60° under 100 psi of hydrogen for 2 hours. Toluene (100 mL) was added and the mixture was concentrated to an oil weighing 75 g. the mixture was concentrated to an oil

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

Procedure: In a manner similar to that described in the preceding examples, dimethyl 2,6-di-(n-propyl)-4-(4-trifluoromethylphenyl)-1-[2-(2-thienyl)ethyl]-1,4-dihydropyridine-3,5-dicarboxylate is prepared by the reaction of (a) 2-(2-aminoethyl)thiophene and methyl butyrylacetate to obtain methyl 3-[2-(2-thienyl)ethyl]amino-2-hexenoate and (b) reacting the ester so obtained with 4-trifluoromethylbenzaldehyde in the presence of 2-(2-aminoethyl)thiophene and titanium tetrachloride.

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

Procedure: In a manner similar to that described in the preceding examples, dimethyl 2,6-di-(n-propyl)-4-(4-trifluoromethylphenyl)-1-[2-(2-thienyl)ethyl]-1,4-dihydropyridine-3,5-dicarboxylate is prepared by the reaction of (a) 2-(2-aminoethyl)thiophene and methyl butyrylacetate to obtain methyl 3-[2-(2-thienyl)ethyl]amino-2-hexenoate and (b) reacting the ester so obtained with 4-trifluoromethylbenzaldehyde in the presence of 2-(2-aminoethyl)thiophene and titanium tetrachloride.

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

Procedure: In a manner similar to that described in the preceding examples, dimethyl 2,6-di-(n-propyl)-4-(4-trifluoromethylphenyl)-1-[2-(2-thienyl)ethyl]-1,4-dihydropyridine-3,5-dicarboxylate is prepared by the reaction of (a) 2-(2-aminoethyl)thiophene and methyl butyrylacetate to obtain methyl 3-[2-(2-thienyl)ethyl]amino-2-hexenoate and (b) reacting the ester so obtained with 4-trifluoromethylbenzaldehyde in the presence of 2-(2-aminoethyl)thiophene and titanium tetrachloride.