methyl 3,3-dimethylbutanoate

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:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of lithium di-isopropylamide, prepared by addition of 8.33 mL (20 mmol) of 2.4 M n-butyllithium in hexane to a 0° C. solution of 3.40 g (20 mmol) of di-isopropylamine in 50 mL of dry THF, is cooled to -78° C. and to it is added dropwise over 30 min a solution of 2.60 g (20 mmol) of methyl t-butylacetate in 50 mL of dry THF. The mixture is stirred at -78° C. for 1 h, then 18.8 g (100 mmol) of 1,2-dibromoethane and 10 mL of HMPA is added all at once. The mixture is stirred for 4 h at -78° C., then allowed to warm slowly to room temperature. Water (100 mL) is carefully added, and the mixture is then extracted with three 100-mL portions of hexane. The combined organic extract is washed with water (100 mL) then with satd. NaCl (50 mL) and dried over Na2SO4. The solvent is removed and the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation. The ester is hydrolyzed by refluxing for 2 h with 25 mL (50 mmol) of 2 N NaOH, the water is removed in Vacuo, and the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer, connected to a distillation apparatus, and heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring. The distillate is collected and the reaction is terminated when di-n-butylphthalate begins to reflux in the still head. The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation. The mixture is stirred for 4 h at -78° C. to warm slowly to room temperature the mixture is then extracted with three 100-mL portions of hexane The combined organic extract is washed with water (100 mL) NaCl (50 mL) and dried over Na2SO4 The solvent is removed the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation the water is removed in Vacuo the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring The distillate is collected the reaction is terminated when di-n-butylphthalate to reflux in the still head The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of lithium di-isopropylamide, prepared by addition of 8.33 mL (20 mmol) of 2.4 M n-butyllithium in hexane to a 0° C. solution of 3.40 g (20 mmol) of di-isopropylamine in 50 mL of dry THF, is cooled to -78° C. and to it is added dropwise over 30 min a solution of 2.60 g (20 mmol) of methyl t-butylacetate in 50 mL of dry THF. The mixture is stirred at -78° C. for 1 h, then 18.8 g (100 mmol) of 1,2-dibromoethane and 10 mL of HMPA is added all at once. The mixture is stirred for 4 h at -78° C., then allowed to warm slowly to room temperature. Water (100 mL) is carefully added, and the mixture is then extracted with three 100-mL portions of hexane. The combined organic extract is washed with water (100 mL) then with satd. NaCl (50 mL) and dried over Na2SO4. The solvent is removed and the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation. The ester is hydrolyzed by refluxing for 2 h with 25 mL (50 mmol) of 2 N NaOH, the water is removed in Vacuo, and the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer, connected to a distillation apparatus, and heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring. The distillate is collected and the reaction is terminated when di-n-butylphthalate begins to reflux in the still head. The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation. The mixture is stirred for 4 h at -78° C. to warm slowly to room temperature the mixture is then extracted with three 100-mL portions of hexane The combined organic extract is washed with water (100 mL) NaCl (50 mL) and dried over Na2SO4 The solvent is removed the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation the water is removed in Vacuo the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring The distillate is collected the reaction is terminated when di-n-butylphthalate to reflux in the still head The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of methyl 3,3-dimethylbutanoate (500 mg, 3.84 mmol) in EtOH (12 ml) was added hydrazine monohydrate (1.87 ml, 38.4 mmol). The mixture was heated to 80° C. under reflux for overnight. The reaction was cooled back down to room temperature and concentrated to dryness affording a crude residue. The residue was dried under high vacuum to afford the title compound as crystalline solid (90 mg, 18% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.69-9.12 (s, 1H) 4.13 (br. s, 2H) 1.89 (s, 2H) 0.94 (s, 9H). under reflux for overnight The reaction was cooled back down to room temperature concentrated to dryness affording a crude residue The residue was dried under high vacuum

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of methyl 3,3-dimethylbutanoate (500 mg, 3.84 mmol) in EtOH (12 ml) was added hydrazine monohydrate (1.87 ml, 38.4 mmol). The mixture was heated to 80° C. under reflux for overnight. The reaction was cooled back down to room temperature and concentrated to dryness affording a crude residue. The residue was dried under high vacuum to afford the title compound as crystalline solid (90 mg, 18% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.69-9.12 (s, 1H) 4.13 (br. s, 2H) 1.89 (s, 2H) 0.94 (s, 9H). under reflux for overnight The reaction was cooled back down to room temperature concentrated to dryness affording a crude residue The residue was dried under high vacuum

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of lithium di-isopropylamide, prepared by addition of 8.33 mL (20 mmol) of 2.4 M n-butyllithium in hexane to a 0° C. solution of 3.40 g (20 mmol) of di-isopropylamine in 50 mL of dry THF, is cooled to -78° C. and to it is added dropwise over 30 min a solution of 2.60 g (20 mmol) of methyl t-butylacetate in 50 mL of dry THF. The mixture is stirred at -78° C. for 1 h, then 18.8 g (100 mmol) of 1,2-dibromoethane and 10 mL of HMPA is added all at once. The mixture is stirred for 4 h at -78° C., then allowed to warm slowly to room temperature. Water (100 mL) is carefully added, and the mixture is then extracted with three 100-mL portions of hexane. The combined organic extract is washed with water (100 mL) then with satd. NaCl (50 mL) and dried over Na2SO4. The solvent is removed and the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation. The ester is hydrolyzed by refluxing for 2 h with 25 mL (50 mmol) of 2 N NaOH, the water is removed in Vacuo, and the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer, connected to a distillation apparatus, and heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring. The distillate is collected and the reaction is terminated when di-n-butylphthalate begins to reflux in the still head. The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation. The mixture is stirred for 4 h at -78° C. to warm slowly to room temperature the mixture is then extracted with three 100-mL portions of hexane The combined organic extract is washed with water (100 mL) NaCl (50 mL) and dried over Na2SO4 The solvent is removed the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation the water is removed in Vacuo the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring The distillate is collected the reaction is terminated when di-n-butylphthalate to reflux in the still head The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation

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

実験手順: In a 500 mL dried round-bottom flask, acetonitrile (6.31, 153.6 mmol) dissolved in THF (50 mL) was treated with LiHMDS (156.3 mL, 1.0 M solution in THF) at −78° C. To this solution was added methyl 3,3-dimethylbutanoate in THF (50 mL) at −78° C. The solution was warmed to rt, and NaHCO3 (100 mL, saturated solution) was added. The layers were separated and the aqueous layer was extracted with ether (3×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the desired product, which was used in the next step without purification. 1H NMR (300 MHz, CD2Cl2) δ 3.47 (s, 2H), 2.44 (s, 2H), 1.03 (s, 9H). The layers were separated the aqueous layer was extracted with ether (3×100 mL) The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of methyl 3,3-dimethylbutanoate (500 mg, 3.84 mmol) in EtOH (12 ml) was added hydrazine monohydrate (1.87 ml, 38.4 mmol). The mixture was heated to 80° C. under reflux for overnight. The reaction was cooled back down to room temperature and concentrated to dryness affording a crude residue. The residue was dried under high vacuum to afford the title compound as crystalline solid (90 mg, 18% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.69-9.12 (s, 1H) 4.13 (br. s, 2H) 1.89 (s, 2H) 0.94 (s, 9H). under reflux for overnight The reaction was cooled back down to room temperature concentrated to dryness affording a crude residue The residue was dried under high vacuum

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of lithium di-isopropylamide, prepared by addition of 8.33 mL (20 mmol) of 2.4 M n-butyllithium in hexane to a 0° C. solution of 3.40 g (20 mmol) of di-isopropylamine in 50 mL of dry THF, is cooled to -78° C. and to it is added dropwise over 30 min a solution of 2.60 g (20 mmol) of methyl t-butylacetate in 50 mL of dry THF. The mixture is stirred at -78° C. for 1 h, then 18.8 g (100 mmol) of 1,2-dibromoethane and 10 mL of HMPA is added all at once. The mixture is stirred for 4 h at -78° C., then allowed to warm slowly to room temperature. Water (100 mL) is carefully added, and the mixture is then extracted with three 100-mL portions of hexane. The combined organic extract is washed with water (100 mL) then with satd. NaCl (50 mL) and dried over Na2SO4. The solvent is removed and the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation. The ester is hydrolyzed by refluxing for 2 h with 25 mL (50 mmol) of 2 N NaOH, the water is removed in Vacuo, and the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer, connected to a distillation apparatus, and heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring. The distillate is collected and the reaction is terminated when di-n-butylphthalate begins to reflux in the still head. The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation. The mixture is stirred for 4 h at -78° C. to warm slowly to room temperature the mixture is then extracted with three 100-mL portions of hexane The combined organic extract is washed with water (100 mL) NaCl (50 mL) and dried over Na2SO4 The solvent is removed the product, methyl 2-t-butyl-4-bromobutyrate, is purified by vacuum distillation the water is removed in Vacuo the residue is suspended in 25 ml of di-n-butylphthalate in a 200 mL round-bottomed flask with an efficient stirrer heated slowly under vacuum (0.5 torr) in an oil bath to 180° C. with vigorous stirring The distillate is collected the reaction is terminated when di-n-butylphthalate to reflux in the still head The product, α-t-butyl-γ-butyrolactone, is then purified by vacuum distillation