1-BOC-2-甲基肼

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]-2-methylpropanoyl chloride (5.3 g, 22 mmole) in 40 ml of dry tetrahydrofuran was treated with triethylamine (4.10 ml, 30 mmole) and 4-(N,N-dimethylamino)pyridine (5 mg). A solution of 1-[(1,1-dimethylethoxy)carbonyl]-2-methylhydrazine (2.90 g, 20 mmole) in 20 ml of tetrahydrofuran was added dropwise at 0° C. and the resulting mixture was stirred at 20° C. overnight. The solvent was evaporated and the solid residue was partitioned between ethyl acetate and water. The organic phase was washed successively with 0.5N hydrochloric acid, 5% sodium bicarbonate, and water. Drying over magnesium sulfate and evaporation gave 6.6 g of the title compound as a colorless solid, m.p. 140°-145° C. The solvent was evaporated the solid residue was partitioned between ethyl acetate and water The organic phase was washed successively with 0.5N hydrochloric acid, 5% sodium bicarbonate, and water Drying over magnesium sulfate and evaporation

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]-2-methylpropanoyl chloride (5.3 g, 22 mmole) in 40 ml of dry tetrahydrofuran was treated with triethylamine (4.10 ml, 30 mmole) and 4-(N,N-dimethylamino)pyridine (5 mg). A solution of 1-[(1,1-dimethylethoxy)carbonyl]-2-methylhydrazine (2.90 g, 20 mmole) in 20 ml of tetrahydrofuran was added dropwise at 0° C. and the resulting mixture was stirred at 20° C. overnight. The solvent was evaporated and the solid residue was partitioned between ethyl acetate and water. The organic phase was washed successively with 0.5N hydrochloric acid, 5% sodium bicarbonate, and water. Drying over magnesium sulfate and evaporation gave 6.6 g of the title compound as a colorless solid, m.p. 140°-145° C. The solvent was evaporated the solid residue was partitioned between ethyl acetate and water The organic phase was washed successively with 0.5N hydrochloric acid, 5% sodium bicarbonate, and water Drying over magnesium sulfate and evaporation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-[(1,1-dimethylethoxy)carbonyl]-2-[(phenylmethoxy)carbonyl]-2-methylhydrazine (15.0 g, 53. mmole) in 100 ml of methanol containing 4.9 ml of concentrated hydrochloric acid was hydrogenated at 1 atm in the presence of 3.0 g of 10% palladium-on-charcoal catalyst for 1 hour. The catalyst was filtered and the solvents were removed in vacuo. The residue was dissolved in water, the pH adjusted to 8.0 with sodium hydroxide and the mixture was extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and evaporated to give 5.6 g of the title compound as a colorless solid, m.p. 50° C. The catalyst was filtered the solvents were removed in vacuo The residue was dissolved in water the mixture was extracted with ethyl acetate The organic phase was dried over magnesium sulfate evaporated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (R)-benzyl 3-(4-(benzyloxy)phenyl)-2-hydroxypropanoate (Compound XLIII-1) 1.81 g (5.00 mmol) and 2,6-lutidine 874 μl (7.50 mmol) in dichloromethane 15 ml, trifluoromethanesulfonic anhydride 1.26 ml (7.50 mmol) was added and the mixture was stirred at 0° C. for 0.5 hr. N-tert-butoxycarbonyl-N′-methylhydrazine (Compound XXXIV-1) 1.46 g (10.0 mol) was added to the solution mixture and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate 100 ml and washed with water 100 ml. The organic phase was washed with brine 100 ml and dried over magnesium sulfate and filtered. The mother solution was concentrated in vacuo and the residue was purified on silica gel column chromatography (Merck 60N spherical, neutral elution by chloroform) to obtain the title compound 0.97 g (17.3%). the mixture was stirred at room temperature overnight washed with water 100 ml The organic phase was washed with brine 100 ml dried over magnesium sulfate filtered The mother solution was concentrated in vacuo the residue was purified on silica gel column chromatography (Merck 60N spherical, neutral elution by chloroform)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (R)-benzyl 3-(4-(benzyloxy)phenyl)-2-hydroxypropanoate (Compound XLIII-1) 1.81 g (5.00 mmol) and 2,6-lutidine 874 μl (7.50 mmol) in dichloromethane 15 ml, trifluoromethanesulfonic anhydride 1.26 ml (7.50 mmol) was added and the mixture was stirred at 0° C. for 0.5 hr. N-tert-butoxycarbonyl-N′-methylhydrazine (Compound XXXIV-1) 1.46 g (10.0 mol) was added to the solution mixture and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate 100 ml and washed with water 100 ml. The organic phase was washed with brine 100 ml and dried over magnesium sulfate and filtered. The mother solution was concentrated in vacuo and the residue was purified on silica gel column chromatography (Merck 60N spherical, neutral elution by chloroform) to obtain the title compound 0.97 g (17.3%). the mixture was stirred at room temperature overnight washed with water 100 ml The organic phase was washed with brine 100 ml dried over magnesium sulfate filtered The mother solution was concentrated in vacuo the residue was purified on silica gel column chromatography (Merck 60N spherical, neutral elution by chloroform)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under argon and at RT, 17.1 g (53.4 mmol, 1.3 eq.) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate and 21.4 ml (123.1 mol, 3.0 eq.) of N,N-diisopropylethylamine were added to a solution of 9.1 g (49.3 mmol, 1.2 eq.) of 2-fluoro-4-nitrobenzoic acid in 200 ml of DMF, and the mixture was stirred at RT for 20 min. A solution of 12.5 g (purity 48%, 41 mmol) of tert-butyl 2-methylhydrazinecarboxylate in 50 ml of DMF was added, and the reaction mixture was stirred at RT for 6 h. After removal of the DMF under reduced pressure and addition of water/ethyl acetate and phase separation, the organic phase was washed with 10% aqueous citric acid and with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel 60, mobile phase: cyclohexane/ethyl acetate mixtures). Yield: 8.35 g (65% of theory) the reaction mixture was stirred at RT for 6 h After removal of the DMF under reduced pressure and addition of water/ethyl acetate and phase separation the organic phase was washed with 10% aqueous citric acid and with saturated aqueous sodium chloride solution dried (sodium sulphate) filtered concentrated under reduced pressure The crude product was purified by flash chromatography (silica gel 60, mobile phase: cyclohexane/ethyl acetate mixtures)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 24.8 g (70.8 mmol) of 1-benzyl 2-tert-butyl 1-methylhydrazine-1,2-dicarboxylate in 500 ml of ethanol was hydrogenated in the presence of 1.24 g of palladium (10% on activated carbon) at RT and standard pressure. The reaction mixture was then filtered through Celite and the filtrate was concentrated under reduced pressure and dried. Yield: 12.3 g (purity 48%, 57% of theory) The reaction mixture was then filtered through Celite the filtrate was concentrated under reduced pressure dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under argon and at RT, 17.1 g (53.4 mmol, 1.3 eq.) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate and 21.4 ml (123.1 mol, 3.0 eq.) of N,N-diisopropylethylamine were added to a solution of 9.1 g (49.3 mmol, 1.2 eq.) of 2-fluoro-4-nitrobenzoic acid in 200 ml of DMF, and the mixture was stirred at RT for 20 min. A solution of 12.5 g (purity 48%, 41 mmol) of tert-butyl 2-methylhydrazinecarboxylate in 50 ml of DMF was added, and the reaction mixture was stirred at RT for 6 h. After removal of the DMF under reduced pressure and addition of water/ethyl acetate and phase separation, the organic phase was washed with 10% aqueous citric acid and with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel 60, mobile phase: cyclohexane/ethyl acetate mixtures). Yield: 8.35 g (65% of theory) the reaction mixture was stirred at RT for 6 h After removal of the DMF under reduced pressure and addition of water/ethyl acetate and phase separation the organic phase was washed with 10% aqueous citric acid and with saturated aqueous sodium chloride solution dried (sodium sulphate) filtered concentrated under reduced pressure The crude product was purified by flash chromatography (silica gel 60, mobile phase: cyclohexane/ethyl acetate mixtures)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 24.8 g (70.8 mmol) of 1-benzyl 2-tert-butyl 1-methylhydrazine-1,2-dicarboxylate in 500 ml of ethanol was hydrogenated in the presence of 1.24 g of palladium (10% on activated carbon) at RT and standard pressure. The reaction mixture was then filtered through Celite and the filtrate was concentrated under reduced pressure and dried. Yield: 12.3 g (purity 48%, 57% of theory) The reaction mixture was then filtered through Celite the filtrate was concentrated under reduced pressure dried

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-(t-Butoxycarbonyl)-N′-methylhydrazine (100 mmol) (Lenman, et al., J. Chem. Soc. Perkin Trans., 1997, 16, 2297-2312; Dutta, et al., J. Chem. Soc. Perkin Trans., 1986, 1655-1664) was added to 3-isochromanone (7.4 g, 50 mmol) (Cheng, et al., J. Heterocyclic Chem., 1995, 32, 73) in a sealed tube followed by 0.2 mL of acetic acid and heated for 12 h at 100° C. The reaction mixture was diluted with EtOAc (100 mL), washed with water (50 mL),1 M HCl (50 mL), brine (50 mL) and dried (Na2SO4). The desired alcohol 2-[2-[2-(Hydroxymethyl)phenyl]-1-oxoethyl]-2-methylhydrazinecarboxylic acid, 1,1-dimethylethyl ester was purified by flash chromatography (silica) using 50% EtOAc in hexane as eluent. MS (ESI) 295 (M+H). washed with water (50 mL),1 M HCl (50 mL), brine (50 mL) dried (Na2SO4) The desired alcohol 2-[2-[2-(Hydroxymethyl)phenyl]-1-oxoethyl]-2-methylhydrazinecarboxylic acid, 1,1-dimethylethyl ester was purified by flash chromatography (silica)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-[(1,1-dimethylethoxy)carbonyl]-2-[(phenylmethoxy)carbonyl]-2-methylhydrazine (15.0 g, 53. mmole) in 100 ml of methanol containing 4.9 ml of concentrated hydrochloric acid was hydrogenated at 1 atm in the presence of 3.0 g of 10% palladium-on-charcoal catalyst for 1 hour. The catalyst was filtered and the solvents were removed in vacuo. The residue was dissolved in water, the pH adjusted to 8.0 with sodium hydroxide and the mixture was extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and evaporated to give 5.6 g of the title compound as a colorless solid, m.p. 50° C. The catalyst was filtered the solvents were removed in vacuo The residue was dissolved in water the mixture was extracted with ethyl acetate The organic phase was dried over magnesium sulfate evaporated

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]-2-methylpropanoyl chloride (5.3 g, 22 mmole) in 40 ml of dry tetrahydrofuran was treated with triethylamine (4.10 ml, 30 mmole) and 4-(N,N-dimethylamino)pyridine (5 mg). A solution of 1-[(1,1-dimethylethoxy)carbonyl]-2-methylhydrazine (2.90 g, 20 mmole) in 20 ml of tetrahydrofuran was added dropwise at 0° C. and the resulting mixture was stirred at 20° C. overnight. The solvent was evaporated and the solid residue was partitioned between ethyl acetate and water. The organic phase was washed successively with 0.5N hydrochloric acid, 5% sodium bicarbonate, and water. Drying over magnesium sulfate and evaporation gave 6.6 g of the title compound as a colorless solid, m.p. 140°-145° C. The solvent was evaporated the solid residue was partitioned between ethyl acetate and water The organic phase was washed successively with 0.5N hydrochloric acid, 5% sodium bicarbonate, and water Drying over magnesium sulfate and evaporation