3-methyloxolan-2-one

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:100.01; pressure:0.00; stir:

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

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

Procedure: Under an argon atmosphere, n-butyllithium (1.7 M in hexane, 1800 ml, 3.06 mole) was added slowly to a stirred solution of diisopropylamine (309.4 g, 3.06 mole) in tetrahydrofuran (1800 ml) at -78° C. Upon completion of addition, the reaction mixture was allowed to stir for 30 minutes at which time alpha-methyl-gamma-butyrolactone (278.0 g, 2.78 mole) was added dropwise, also at -78° C. The reaction mixture was stirred 30 minutes then dimethyl disulfide (392.8 g, 4.17 mole) was added dropwise. After stirring for 30 minutes at -78° C., the reaction mixture was warmed to ambient temperature during a one hour period. The reaction mixture was quenched with 5% aqueous hydrochloric acid (1500 ml) and then diluted with ethyl acetate (2000 ml). The layers were separated, and the organic layer was washed with aqueous 10% hydrochloric acid (1×200 ml) and then saturated aqueous sodium bicarbonate (1×100 ml). The organic layer was dried and concentrated under reduced pressure. The residue was distilled to yield 234.6 g of alpha-methyl-alpha-methylthio-gamma-butyrolactone as a colorless oil, b.p. 104°-105° C./8 mm Hg. The NMR spectrum was consistent with the proposed structure. Upon completion of addition was added dropwise, also at -78° C After stirring for 30 minutes at -78° C. The reaction mixture was quenched with 5% aqueous hydrochloric acid (1500 ml) diluted with ethyl acetate (2000 ml) The layers were separated the organic layer was washed with aqueous 10% hydrochloric acid (1×200 ml) The organic layer was dried concentrated under reduced pressure The residue was distilled

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

Procedure: Following the general procedure described in A. R. Friedman, D. S. Payne and A. R. Day, J. Heterocyclic Chemistry, 3:257-259(1966), a mixture of 9 g of 1,2-phenylenediamine dihydrochloride and 7 g of 2-methylbutyrolactone in 60 mL of 4N hydrochloric acid was heated to reflux for 4 days, 1 teaspoon of decolorizing carbon added, and after another 15 min reflux, filtered hot. The filtrate was concentrated under reduced pressure to near dryness, the residue made basic (pH=8) with ammonium hydroxide and extracted into 3×100 mL of ethyl acetate. The combined extracts were dried over magnesium sulfate and concentrated under reduced pressure. After drying under vacuum, 12 g of 3-(1H-benzimidazol-2-yl)-butan-1-ol was obtained as a resin. was heated to reflux for 4 days 1 teaspoon of decolorizing carbon added after another 15 min reflux filtered hot The filtrate was concentrated under reduced pressure extracted into 3×100 mL of ethyl acetate The combined extracts were dried over magnesium sulfate concentrated under reduced pressure After drying under vacuum

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.05 mmol RuHCi(H2)(PCy3)2, 0.54 mmol methyl-3-cyanoisobutyrate (prepared by addition of HCN to methyl methacrylate), 17.7 g THF, 15.3 g water, and 0.0596 g cyclododecane (internal standard for gc analysis) was stirred in an autoclave and heated to 100° C. under 7000 kPa H2. After 3.2 hours, the nitrile was completely and cleanly converted to methyl-butyrolactone, which formed by transesterification/cyclization of the intermediate hydroxyester, methyl 2-methyl-4-hydroxybutyrate.

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

Procedure: Under an argon atmosphere, n-butyllithium (1.7 M in hexane, 1800 ml, 3.06 mole) was added slowly to a stirred solution of diisopropylamine (309.4 g, 3.06 mole) in tetrahydrofuran (1800 ml) at -78° C. Upon completion of addition, the reaction mixture was allowed to stir for 30 minutes at which time alpha-methyl-gamma-butyrolactone (278.0 g, 2.78 mole) was added dropwise, also at -78° C. The reaction mixture was stirred 30 minutes then dimethyl disulfide (392.8 g, 4.17 mole) was added dropwise. After stirring for 30 minutes at -78° C., the reaction mixture was warmed to ambient temperature during a one hour period. The reaction mixture was quenched with 5% aqueous hydrochloric acid (1500 ml) and then diluted with ethyl acetate (2000 ml). The layers were separated, and the organic layer was washed with aqueous 10% hydrochloric acid (1×200 ml) and then saturated aqueous sodium bicarbonate (1×100 ml). The organic layer was dried and concentrated under reduced pressure. The residue was distilled to yield 234.6 g of alpha-methyl-alpha-methylthio-gamma-butyrolactone as a colorless oil, b.p. 104°-105° C./8 mm Hg. The NMR spectrum was consistent with the proposed structure. Upon completion of addition was added dropwise, also at -78° C After stirring for 30 minutes at -78° C. The reaction mixture was quenched with 5% aqueous hydrochloric acid (1500 ml) diluted with ethyl acetate (2000 ml) The layers were separated the organic layer was washed with aqueous 10% hydrochloric acid (1×200 ml) The organic layer was dried concentrated under reduced pressure The residue was distilled

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-methyldihydrofuran-2(3H)-one (2.0 g), thionyl chloride (1.5 ml) and zinc chloride (10 mg) was stirred at 80° C. for 15 hours. The mixture was cooled to room temperature, and the reaction mixture was added dropwise to a solution of 4-benzylpiperazin-1-amine (3.8 g) in THF (50 mL) at 0° C., followed by stirring at 0° C. for 2 hours. Sodium hydride (60% in oil; 2.4 g) was added thereto and the mixture was stirred at room temperature for 15 hours. Ice was added thereto, and then the reaction mixture was concentrated under reduced pressure. The residue was diluted with water, and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained was purified by basic silica gel column chromatography (ethyl acetate/hexane=1/5) to obtain the title compound (2.0 g, 37%) as a yellow oil. The mixture was cooled to room temperature by stirring at 0° C. for 2 hours the mixture was stirred at room temperature for 15 hours Ice was added the reaction mixture was concentrated under reduced pressure The residue was diluted with water extracted with dichloromethane The extract was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue obtained was purified by basic silica gel column chromatography (ethyl acetate/hexane=1/5)

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

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