乙酰乙酰苄胺

反应条件: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-benzyl-3-oxobutanamide (compound A 100 g, 522.9 mmol) in dichloromethane (500 ml) at 0-5° C. was added dropwise a solution of bromine (25.55 ml, 575.2 mmol) over 6 h. The reaction mixture was warmed up to 20-25° C. and stirred for 2 hours (bromine colour disappeared). An aqueous solution (600 mL) of sodium bicarbonate (65.9 g, 784.44 mmol) was added to the mixture. The organic layer was separated, washed with brine (200 mL), and then evaporated to dryness to give N-benzyl-4-bromo-3-oxobutanamide (114.25 g, quantitative) and was used in the next step without further purification. The organic layer was separated washed with brine (200 mL) evaporated to dryness

反应条件: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-benzyl-3-oxobutanamide (compound A 100 g, 522.9 mmol) in dichloromethane (500 ml) at 0-5° C. was added dropwise a solution of bromine (25.55 ml, 575.2 mmol) over 6 h. The reaction mixture was warmed up to 20-25° C. and stirred for 2 hours (bromine colour disappeared). An aqueous solution (600 mL) of sodium bicarbonate (65.9 g, 784.44 mmol) was added to the mixture. The organic layer was separated, washed with brine (200 mL), and then evaporated to dryness to give N-benzyl-4-bromo-3-oxobutanamide (114.25 g, quantitative) and was used in the next step without further purification. The organic layer was separated washed with brine (200 mL) evaporated to dryness

反应条件: temp:7.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-benzyl-3-oxobutanamide (compound A 50 g, 261 mmol) in dichloromethane (350 ml) was added bromine (14.82 ml, 288 mmol) at 0-5° C., then stirred at 20-25° C. for 3 hours (bromine colour disappeared). Water (300 ml) was added to the mixture with stirring, stirred for 10 min. Organic phase was separated, washed with sodium bicarbonate solution, dried, evaporated to dryness (compound B). The solid residue (compound B) dissolved in methanol (900 ml), added potassium formate (44.0 g, 523 mmol) and the mixture was heated under reflux for 2 hours. Methanol was removed on a rotavap, the residue was taken up into ethyl acetate (EA) (500 ml) under reflux, filtered hot, the filter cake washed with warm EA (100 ml). The combined filtrate was cooled to 5-10° C., aged for 1.5 hours. The precipitate was collected, washed with cold EA (50 ml), dried to give 25 g (46.1%) of crude product, light beige. Re-crystallised from water (300 ml), with active carbon (1 g). Filtered hot on celite, cooled in ice, aged for 1 hour, crystals collected, washed with cold water (20 ml), dried on air overnight to give N-benzyl-4-hydroxy-3-oxobutanamide (21 g, 101 mmol, 38.8% yield). stirred for 10 min Organic phase was separated washed with sodium bicarbonate solution dried evaporated to dryness (compound B) The solid residue (compound B) dissolved in methanol (900 ml) the mixture was heated under reflux for 2 hours Methanol was removed on a rotavap under reflux filtered hot the filter cake washed with warm EA (100 ml) The precipitate was collected washed with cold EA (50 ml) dried to give 25 g (46.1%) of crude product Filtered hot on celite cooled in ice aged for 1 hour crystals collected washed with cold water (20 ml) dried on air overnight

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

实验步骤: 7.27 g (0.038) of N-benzyl-3-oxobutyramide were dissolved in a solution of 5.32 g (0.133 mol) of NaOH in 58 ml of water. To the ice-cooled stirred solution, 0.040 mol of phenyldiazonium chloride were added dropwise at such a rate as to keep the temperature at 0° C. The precipitated solid was filtered and recrystallised from MeOH yielding 9 g of the title compound. M.p.=101°-103° C. were added dropwise at such a rate as at 0° C The precipitated solid was filtered recrystallised from MeOH yielding 9 g of the title compound

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

实验步骤: 9 ml (0.05 mol) of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (diketene-acetone adduct) were added dropwise to a solution of 5.5 ml (0.05 mol) of benzylamine in 20 ml of toluene and the temperature was allowed to rise 70° C. The solution was refluxed for 2 h then the solvent was removed in vacuo. The crude product was triturated with ether obtaining 7.5 g of the title compound. M.p.=84°-86° C. to rise 70° C The solution was refluxed for 2 h the solvent was removed in vacuo The crude product was triturated with ether obtaining 7.5 g of the title compound

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

实验步骤: 7.27 g (0.038) of N-benzyl-3-oxobutyramide were dissolved in a solution of 5.32 g (0.133 mol) of NaOH in 58 ml of water. To the ice-cooled stirred solution, 0.040 mol of phenyldiazonium chloride were added dropwise at such a rate as to keep the temperature at 0° C. The precipitated solid was filtered and recrystallised from MeOH yielding 9 g of the title compound. M.p.=101°-103° C. were added dropwise at such a rate as at 0° C The precipitated solid was filtered recrystallised from MeOH yielding 9 g of the title compound

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

实验步骤: 9 ml (0.05 mol) of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (diketene-acetone adduct) were added dropwise to a solution of 5.5 ml (0.05 mol) of benzylamine in 20 ml of toluene and the temperature was allowed to rise 70° C. The solution was refluxed for 2 h then the solvent was removed in vacuo. The crude product was triturated with ether obtaining 7.5 g of the title compound. M.p.=84°-86° C. to rise 70° C The solution was refluxed for 2 h the solvent was removed in vacuo The crude product was triturated with ether obtaining 7.5 g of the title compound

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

实验步骤: To a solution of N-benzyl-3-oxobutanamide (100.00 g, 522.93 mmol), K2CO3 (216.50 g, 1568.79 mmol) in DMF (1 L) was added 1,4-dibromobutane (169.36 g, 784.4 mmol) dropwise at rt. After addition, the reaction mixture was stirred at rt overnight and concentrated in vacuo. The residue was added water (500 mL) and extracted with EtOAc (500 mL×3). The combined organic phases were washed with brine (500 mL×3), dried over anhydrous Na2SO4, then filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/8) to give the product as a white solid (69.50 g, 54%). After addition concentrated in vacuo The residue was added water (500 mL) extracted with EtOAc (500 mL×3) The combined organic phases were washed with brine (500 mL×3) dried over anhydrous Na2SO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/8)

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

实验步骤: To a solution of 4-methyleneoxetan-2-one (60.00 g, 713.69 mmol) in DCM (600 mL) was added phenylmethanamine (91.76 g, 856.43 mmol) dropwise at 0° C. After addition, the reaction mixture was stirred at rt overnight and concentrated in vacuo. The residue was beaten with a mixture of PE and EtOAc (10/1 (v/v), 200 mL) for 1 h and filtered. The filter cake was washed with a mixture of PE and EtOAc (10/1 (v/v), 100 mL) to give the title compound as a yellow solid (136.38 g, 100%). After addition concentrated in vacuo The residue was beaten with a mixture of PE and EtOAc (10/1 (v/v), 200 mL) for 1 h filtered The filter cake was washed with a mixture of PE and EtOAc (10/1 (v/v), 100 mL)

反应条件: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-benzyl-3-oxobutanamide (compound A 100 g, 522.9 mmol) in dichloromethane (500 ml) at 0-5° C. was added dropwise a solution of bromine (25.55 ml, 575.2 mmol) over 6 h. The reaction mixture was warmed up to 20-25° C. and stirred for 2 hours (bromine colour disappeared). An aqueous solution (600 mL) of sodium bicarbonate (65.9 g, 784.44 mmol) was added to the mixture. The organic layer was separated, washed with brine (200 mL), and then evaporated to dryness to give N-benzyl-4-bromo-3-oxobutanamide (114.25 g, quantitative) and was used in the next step without further purification. The organic layer was separated washed with brine (200 mL) evaporated to dryness

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

实验步骤: 7.27 g (0.038) of N-benzyl-3-oxobutyramide were dissolved in a solution of 5.32 g (0.133 mol) of NaOH in 58 ml of water. To the ice-cooled stirred solution, 0.040 mol of phenyldiazonium chloride were added dropwise at such a rate as to keep the temperature at 0° C. The precipitated solid was filtered and recrystallised from MeOH yielding 9 g of the title compound. M.p.=101°-103° C. were added dropwise at such a rate as at 0° C The precipitated solid was filtered recrystallised from MeOH yielding 9 g of the title compound

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

实验步骤: 9 ml (0.05 mol) of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (diketene-acetone adduct) were added dropwise to a solution of 5.5 ml (0.05 mol) of benzylamine in 20 ml of toluene and the temperature was allowed to rise 70° C. The solution was refluxed for 2 h then the solvent was removed in vacuo. The crude product was triturated with ether obtaining 7.5 g of the title compound. M.p.=84°-86° C. to rise 70° C The solution was refluxed for 2 h the solvent was removed in vacuo The crude product was triturated with ether obtaining 7.5 g of the title compound