戊酸肼

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

实验步骤: The carboxylic acid from Preparation 2 (1.5 g, 7.3 mmol) was suspended in dichloromethane (40 mL) containing N,N-dimethylformamide (2 drops) and oxalyl chloride (1.27 mL, 14 mmol) in dichloromethane (5 mL) was added dropwise. The mixture was stirred for 5 hours at room temperature and then evaporated under reduced pressure. The residue was suspended in hexane and evaporate (3×20 mL). The residue was dissolved in dichloromethane and cooled to 0° C. and pentanoic acid hydrazide (1.7 g, 14.6 mmol) was added. 1-Methyl-pyrrolidin-2one (1.6 mL, 14.6 mmol) in dichloromethane (10 mL) was added drop wise and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was triturated with diethyl ether. The material obtained was dissolved in water and acidified to pH 2 by addition of 2N hydrochloric acid. The acidic solution was filtered and the filtrate was washed with ethyl acetate (3×20 mL) then basified with sodium carbonate. The solid formed was triturated with diethyl ether and isolated by filtration to give the title compound as a white solid (0.68 g). was added dropwise evaporated under reduced pressure evaporate (3×20 mL) The residue was dissolved in dichloromethane cooled to 0° C. the mixture was stirred at room temperature for 16 hours The solvent was evaporated under reduced pressure the residue was triturated with diethyl ether The material obtained The acidic solution was filtered the filtrate was washed with ethyl acetate (3×20 mL) The solid formed was triturated with diethyl ether isolated by filtration

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

实验步骤: The carboxylic acid from Preparation 2 (1.5 g, 7.3 mmol) was suspended in dichloromethane (40 mL) containing N,N-dimethylformamide (2 drops) and oxalyl chloride (1.27 mL, 14 mmol) in dichloromethane (5 mL) was added dropwise. The mixture was stirred for 5 hours at room temperature and then evaporated under reduced pressure. The residue was suspended in hexane and evaporate (3×20 mL). The residue was dissolved in dichloromethane and cooled to 0° C. and pentanoic acid hydrazide (1.7 g, 14.6 mmol) was added. 1-Methyl-pyrrolidin-2one (1.6 mL, 14.6 mmol) in dichloromethane (10 mL) was added drop wise and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was triturated with diethyl ether. The material obtained was dissolved in water and acidified to pH 2 by addition of 2N hydrochloric acid. The acidic solution was filtered and the filtrate was washed with ethyl acetate (3×20 mL) then basified with sodium carbonate. The solid formed was triturated with diethyl ether and isolated by filtration to give the title compound as a white solid (0.68 g). was added dropwise evaporated under reduced pressure evaporate (3×20 mL) The residue was dissolved in dichloromethane cooled to 0° C. the mixture was stirred at room temperature for 16 hours The solvent was evaporated under reduced pressure the residue was triturated with diethyl ether The material obtained The acidic solution was filtered the filtrate was washed with ethyl acetate (3×20 mL) The solid formed was triturated with diethyl ether isolated by filtration

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

实验步骤: The carboxylic acid from Preparation 2 (1.5 g, 7.3 mmol) was suspended in dichloromethane (40 mL) containing N,N-dimethylformamide (2 drops) and oxalyl chloride (1.27 mL, 14 mmol) in dichloromethane (5 mL) was added dropwise. The mixture was stirred for 5 hours at room temperature and then evaporated under reduced pressure. The residue was suspended in hexane and evaporate (3×20 mL). The residue was dissolved in dichloromethane and cooled to 0° C. and pentanoic acid hydrazide (1.7 g, 14.6 mmol) was added. 1-Methyl-pyrrolidin-2one (1.6 mL, 14.6 mmol) in dichloromethane (10 mL) was added drop wise and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was triturated with diethyl ether. The material obtained was dissolved in water and acidified to pH 2 by addition of 2N hydrochloric acid. The acidic solution was filtered and the filtrate was washed with ethyl acetate (3×20 mL) then basified with sodium carbonate. The solid formed was triturated with diethyl ether and isolated by filtration to give the title compound as a white solid (0.68 g). was added dropwise evaporated under reduced pressure evaporate (3×20 mL) The residue was dissolved in dichloromethane cooled to 0° C. the mixture was stirred at room temperature for 16 hours The solvent was evaporated under reduced pressure the residue was triturated with diethyl ether The material obtained The acidic solution was filtered the filtrate was washed with ethyl acetate (3×20 mL) The solid formed was triturated with diethyl ether isolated by filtration

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

实验步骤: The carboxylic acid from Preparation 2 (1.5 g, 7.3 mmol) was suspended in dichloromethane (40 mL) containing N,N-dimethylformamide (2 drops) and oxalyl chloride (1.27 mL, 14 mmol) in dichloromethane (5 mL) was added dropwise. The mixture was stirred for 5 hours at room temperature and then evaporated under reduced pressure. The residue was suspended in hexane and evaporate (3×20 mL). The residue was dissolved in dichloromethane and cooled to 0° C. and pentanoic acid hydrazide (1.7 g, 14.6 mmol) was added. 1-Methyl-pyrrolidin-2one (1.6 mL, 14.6 mmol) in dichloromethane (10 mL) was added drop wise and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was triturated with diethyl ether. The material obtained was dissolved in water and acidified to pH 2 by addition of 2N hydrochloric acid. The acidic solution was filtered and the filtrate was washed with ethyl acetate (3×20 mL) then basified with sodium carbonate. The solid formed was triturated with diethyl ether and isolated by filtration to give the title compound as a white solid (0.68 g). was added dropwise evaporated under reduced pressure evaporate (3×20 mL) The residue was dissolved in dichloromethane cooled to 0° C. the mixture was stirred at room temperature for 16 hours The solvent was evaporated under reduced pressure the residue was triturated with diethyl ether The material obtained The acidic solution was filtered the filtrate was washed with ethyl acetate (3×20 mL) The solid formed was triturated with diethyl ether isolated by filtration

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

实验步骤: The carboxylic acid from Preparation 1 (1.5 g, 7.3 mmol) was suspended in dichloromethane (40 ml) containing N,N-dimethylformamide (2 drops) and oxalyl chloride (1.27 ml, 14 mmol) in dichloromethane (5 ml) was added drop wise. The mixture was stirred for 5 hours at room temperature and then was evaporated under reduced pressure. The residue was suspended in hexane and evaporated (3×20 ml). The residue was dissolved in dichloromethane and cooled to 0° C. and pentanoic acid hydrazide (1.7 g, 14.6 mmol) was added. 1-Methyl-pyrrolidin-2-one (1.6 ml, 14.6 mmol) in dichloromethane (10 ml) was added drop wise and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was triturated with diethyl ether. The material obtained was dissolved in water and acidified to pH2 by addition of 2N hydrochloric acid. The acidic solution filtered and the filtrate was washed with ethyl acetate (3×20 ml) then basified with sodium carbonate. The solid formed was triturated with diethyl ether and isolated by filtration to give the title compound as a white solid (0.68 g). was added drop wise was evaporated under reduced pressure evaporated (3×20 ml) The residue was dissolved in dichloromethane cooled to 0° C. the mixture was stirred at room temperature for 16 hours The solvent was evaporated under reduced pressure the residue was triturated with diethyl ether The material obtained The acidic solution filtered the filtrate was washed with ethyl acetate (3×20 ml) The solid formed was triturated with diethyl ether isolated by filtration

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

实验步骤: The carboxylic acid from Preparation 1 (1.5 g, 7.3 mmol) was suspended in dichloromethane (40 ml) containing N,N-dimethylformamide (2 drops) and oxalyl chloride (1.27 ml, 14 mmol) in dichloromethane (5 ml) was added drop wise. The mixture was stirred for 5 hours at room temperature and then was evaporated under reduced pressure. The residue was suspended in hexane and evaporated (3×20 ml). The residue was dissolved in dichloromethane and cooled to 0° C. and pentanoic acid hydrazide (1.7 g, 14.6 mmol) was added. 1-Methyl-pyrrolidin-2-one (1.6 ml, 14.6 mmol) in dichloromethane (10 ml) was added drop wise and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was triturated with diethyl ether. The material obtained was dissolved in water and acidified to pH2 by addition of 2N hydrochloric acid. The acidic solution filtered and the filtrate was washed with ethyl acetate (3×20 ml) then basified with sodium carbonate. The solid formed was triturated with diethyl ether and isolated by filtration to give the title compound as a white solid (0.68 g). was added drop wise was evaporated under reduced pressure evaporated (3×20 ml) The residue was dissolved in dichloromethane cooled to 0° C. the mixture was stirred at room temperature for 16 hours The solvent was evaporated under reduced pressure the residue was triturated with diethyl ether The material obtained The acidic solution filtered the filtrate was washed with ethyl acetate (3×20 ml) The solid formed was triturated with diethyl ether isolated by filtration

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

实验步骤: To a solution of 400 g (3.44 mol) of valeric acid hydrazide (Lancaster Synthesis) in 3000 mL of dichloromethane under a nitrogen atmosphere, was added 250 g (2 mol) of anhydrous magnesium sulfate and 310 g (3.88 mol) of butyraldehyde. The reaction was stirred at ambient temperature for 17 h, filtered, and concentrated in vacuo providing 613 g of nearly colorless solid: mp 66.5°-68.0° C.; NMR (CDCl3) δ0.97 (t, J=7Hz, 3H), 0.92 (t, J=7Hz, 3H), 1.31-1.46 (m, 2H), 1.48-1.73 (m, 4H), 2.19-2.28 (m, 2H), 2.62 (t, J=7Hz, 2H), 7.14 (t, J=6Hz, 1H), 9.18 (br s, 1H). This material was dissolved in 3000 mL of ethanol and cooled to 0° C. in an ice bath prior to the addition of 130.1 g (3.44 mol) of sodium borohydride. The reaction was maintained at 0° C. for 3 h and then allowed to slowly warm to ambient temperature overnight. The volatiles were removed in vacuo and the residue dissolved in 1500 mL of water and continuously extracted with ether/dichloromethane (1: 1) overnight. The extracts were dried (Na2SO4) and concentrated in vacuo to give 549 g (93%) of colorless N2 -butyl valeric acid hydrazide: mp 66.0°-67.5° C.; NMR (CDCl3) δ 0.92 (t, J=7Hz, 6H), 1.17-1.52 (m, 6H), 1.56-1.69 (m, 2H), 2.14 (t, J=7Hz, 2H), 2.82 (t, J=7Hz, 2H). filtered concentrated in vacuo providing 613 g of nearly colorless solid cooled to 0° C. in an ice bath The reaction was maintained at 0° C. for 3 h to slowly warm to ambient temperature overnight The volatiles were removed in vacuo the residue dissolved in 1500 mL of water continuously extracted with ether/dichloromethane (1: 1) overnight The extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: To a solution of 400 g (3.44 mol) of valeric acid hydrazide (Lancaster Synthesis) in 3000 mL of dichloromethane under a nitrogen atmosphere, was added 250 g (2 mol) of anhydrous magnesium sulfate and 310 g (3.88 mol) of butyraldehyde. The reaction was stirred at ambient temperature for 17 h, filtered, and concentrated in vacuo providing 613 g of nearly colorless solid: mp 66.5°-68.0° C.; NMR (CDCl3) δ 0.97 (t, J=7Hz, 3H), 0.92 (t, J=7Hz, 3H), 1.31-1.46 (m, 2H), 1.48-1.73 (m, 4H), 2.19-2.28 (m, 2H), 2.62 (t, J=7Hz, 2H), 7.14 (t, J=6Hz, 1H), 9.18 (br s, 1H). This material was dissolved in 3000 mL of ethanol and cooled to 0° C. in an ice bath prior to the addition of 130.1 g (3.44 mol) of sodium borohydride. The reaction was maintained at 0° C. for 3 h and then allowd to slowly warm to ambient temperature overnight. The volatiles were removed in vacuo and the residue dissolved in 1500 mL of water and conninuousiy extracted with ether/dichloromethane (1:1) overnight. The extracts were dried (Na2SO4) and concentrated in vacuo to give 549 g (93%) of colorless N2 -butyl valeric acid hydrazide: mp 66.0°-67.5° C.; NMR (CDCl3) δ0.92 (t, J=7Hz, 6H), 1.17-1.52 (m, 6H), 1.56-1.69 (m, 2H), 2.14 (t, J=7Hz, 2H), 2.82 (t, J=7Hz, 2H). filtered concentrated in vacuo providing 613 g of nearly colorless solid cooled to 0° C. in an ice bath The reaction was maintained at 0° C. for 3 h to slowly warm to ambient temperature overnight The volatiles were removed in vacuo the residue dissolved in 1500 mL of water conninuousiy extracted with ether/dichloromethane (1:1) overnight The extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: To a solution of 400 g (3.44 mol) of valeric acid hydrazide (Lancaster Synthesis) in 3000 mL of dichloromethane under a nitrogen atmosphere, was added 250 g (2 mol) of anhydrous magnesium sulfate and 310 g (3.88 mol) of butyraldehyde. The reaction was stirred at ambient temperature for 17 h, filtered, and concentrated in vacuo providing 613 g of nearly colorless solid: mp 66.5°-68.0° C.; NMR (CDCl3) δ 0.97 (t, J=7Hz, 3H), 0.92 (t, J=7Hz, 3H), 1.31-1.46 (m, 2H), 1.48-1.73 (m, 4H), 2.19-2.28 (m, 2H), 2.62 (t, J=7Hz, 2H), 7.14 (t, J=6Hz, 1H), 9.18 (br s, 1H). This material was dissolved in 3000 mL of ethanol and cooled to 0° C. in an ice bath prior to the addition of 130.1 g (3.44 mol) of sodium borohydride. The reaction was maintained at 0° C. for 3 h and then allowd to slowly warm to ambient temperature overnight. The volatiles were removed in vacuo and the residue dissolved in 1500 mL of water and conninuousiy extracted with ether/dichloromethane (1:1) overnight. The extracts were dried (Na2SO4) and concentrated in vacuo to give 549 g (93%) of colorless N2 -butyl valeric acid hydrazide: mp 66.0°-67.5° C.; NMR (CDCl3) δ0.92 (t, J=7Hz, 6H), 1.17-1.52 (m, 6H), 1.56-1.69 (m, 2H), 2.14 (t, J=7Hz, 2H), 2.82 (t, J=7Hz, 2H). filtered concentrated in vacuo providing 613 g of nearly colorless solid cooled to 0° C. in an ice bath The reaction was maintained at 0° C. for 3 h to slowly warm to ambient temperature overnight The volatiles were removed in vacuo the residue dissolved in 1500 mL of water conninuousiy extracted with ether/dichloromethane (1:1) overnight The extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: To a solution of 400 g (3.44 mol) of valeric acid hydrazide (Lancaster Synthesis) in 3000 mL of dichloromethane under a nitrogen atmosphere, was added 250 g (2 mol) of anhydrous magnesium sulfate and 310 g (3.88 mol) of butyraldehyde. The reaction was stirred at ambient temperature for 17 h, filtered, and concentrated in vacuo providing 613 g of nearly colorless solid: mp 66.5-68.0° C.; NMR (CDCl3) δ 0.97 (t, J=7 Hz, 3H), 0.92 (t, J=7 Hz, 3H), 1.31-1.46 (m, 2H), 1.48-1.73 (m, 4H), 2.19-2.28 (m, 2H), 2.62 (t, J=7 Hz, 2H), 7.14 (t, J=6 Hz, 1H), 9.18 (br s, 1H). This material was dissolved in 3000 mL of ethanol and cooled to 0° C. in an ice bath prior to the addition of 130.1 g (3.44 mol) of sodium borohydride. The reaction was maintained at 0° C. for 3 h and then allowed to slowly warm to ambient temperature overnight. The volatiles were removed in vacuo and the residue dissolved in 1500 mL of water and continuously extracted with ether/dichloromethane (1:1) overnight. The extracts were dried (Na2SO4) and concentrated in vacuo to give 549 g (93%) of colorless N2 -butyl valeric acid hydrazide: mp 66.0-67.5° C.; NMR (CDCl3) δ 0.92 (t, J=7 Hz, 6H), 1.17-1.52 (m, 6H), 1.56-1.69 (m, 2H), 2.14 (t, J=7 Hz, 2H), 2.82 (t, J=7 Hz, 2H). filtered concentrated in vacuo providing 613 g of nearly colorless solid cooled to 0° C. in an ice bath The reaction was maintained at 0° C. for 3 h to slowly warm to ambient temperature overnight The volatiles were removed in vacuo the residue dissolved in 1500 mL of water continuously extracted with ether/dichloromethane (1:1) overnight The extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: To a solution of 400 g (3.44 mol) of valeric acid hydrazide (Lancaster Synthesis) in 3000 mL of dichloromethane under a nitrogen atmosphere, was added 250 g (2 mol) of anhydrous magnesium sulfate and 310 g (3.88 mol) of butyraldehyde. The reaction was stirred at ambient temperature for 17 h, filtered, and concentrated in vacuo providing 613 g of nearly colorless solid: mp 66.5°-68.0° C.; NMR (CDCl3)δ0.97 (t, J=7 Hz, 3 H), 0.92 (t, J=7 Hz, 3 H), 1.31-1.46 (m, 2 H), 1.48-1.73 (m, 4 H), 2.19-2.28 (m, 2 H), 2.62 (t, J=7 Hz, 2 H), 7.14 (t, J=6 Hz, 1 H), 9.18 (br s, 1 H). This material was dissolved in 3000 mL of ethanol and cooled to 0° C. in an ice bath prior to the addition of 130.1 g (3.44 mol) of sodium borohydride. The reaction was maintained at 0° C. for 3 h and then allowd to slowly warm to ambient temperature overnight. The volatiles were removed in vacuo and the residue dissolved in 1500 mL of water and continuously extracted with ether/dichloromethane (1:1) overnight. The extracts were dried (Na2SO4) and concentrated in vacuo to give 549 g (93%) of colorless N2 -butyl valeric acid hydrazide: mp 66.0°-67.5° C.; NMR (CDCl3)δ0.92 (t, J=7 Hz, 6 H), 1.17-1.52 (m, 6 H), 1.56-1.69 (m, 2 H), 2.14 (t, J=7 Hz, 2 H), 2.82 (t, J=7 Hz, 2 H). filtered concentrated in vacuo providing 613 g of nearly colorless solid cooled to 0° C. in an ice bath The reaction was maintained at 0° C. for 3 h to slowly warm to ambient temperature overnight The volatiles were removed in vacuo the residue dissolved in 1500 mL of water continuously extracted with ether/dichloromethane (1:1) overnight The extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: The carboxylic acid from Preparation 2 (1.5 g, 7.3 mmol) was suspended in dichloromethane (40 mL) containing N,N-dimethylformamide (2 drops) and oxalyl chloride (1.27 mL, 14 mmol) in dichloromethane (5 mL) was added dropwise. The mixture was stirred for 5 hours at room temperature and then evaporated under reduced pressure. The residue was suspended in hexane and evaporate (3×20 mL). The residue was dissolved in dichloromethane and cooled to 0° C. and pentanoic acid hydrazide (1.7 g, 14.6 mmol) was added. 1-Methyl-pyrrolidin-2one (1.6 mL, 14.6 mmol) in dichloromethane (10 mL) was added drop wise and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the residue was triturated with diethyl ether. The material obtained was dissolved in water and acidified to pH 2 by addition of 2N hydrochloric acid. The acidic solution was filtered and the filtrate was washed with ethyl acetate (3×20 mL) then basified with sodium carbonate. The solid formed was triturated with diethyl ether and isolated by filtration to give the title compound as a white solid (0.68 g). was added dropwise evaporated under reduced pressure evaporate (3×20 mL) The residue was dissolved in dichloromethane cooled to 0° C. the mixture was stirred at room temperature for 16 hours The solvent was evaporated under reduced pressure the residue was triturated with diethyl ether The material obtained The acidic solution was filtered the filtrate was washed with ethyl acetate (3×20 mL) The solid formed was triturated with diethyl ether isolated by filtration