(R)-N-苄基-4-苯基-2-丁胺

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

实验步骤: In an apparatus fitted with a Dean Stark trap, reflux a solution of 1.0 kg (6.75 mol) of benzylacetone, 725 g (6.75 mol) of benzylamine and 5.0 g of p-toluenesulfonic acid hydrate in 7 liters of benzene for 14 hours. Remove the solvent in vacuo, and dissolve the residue in 6.5 liters of methanol. With cooling and stirring, carefully add 125 g of NaBH4 and stir the mixture for 16 hours at room temperature. Remove the methanol in vacuo, and add 2 liters water and 4 liters benzene, and extract the product into the benzene. After drying (MgSO4), filter and distill (b.p. 145°-150° C./0.5 mm). Dissolve 1,028 g (4.288 mol) of the distillate and 1.23 kg (4.328 mol) of N-p-toluenesulfonyl-(L)-leucine in 7.2 liters of boiling ethanol and allow to cool to room temperature without agitation. Wash the precipitate with a small amount of ice-cold ethanol, recrystallize from 4.8 liters of ethanol, wash with ice-cold ethanol and filter off the solid product that is highly enriched with the salt of the undesired S enantiomer. Combine the mother liquor from the original precipitation and that from the recrystallization, remove the solvent and recover the free base by basifying with 500 ml of 20% aqueous NaOH and extracting with benzene. After drying (MgSO4), filtering and removing the benzene, dissolve the residue [487 g (2.04 mol)] and 346 g (2.06 mol) of N-acetyl-(L)-leucine in 2.0 liters of boiling ethanol and allow the solution to cool to room temperature. Filter and recrystallize once from 1.8 liter of ethanol followed by recrystallization from 4.0 liters of acetonitrile to obtain the desired R salt, m.p. 151°-152° C. Basify with 400 ml of aqueous 2.5N NaOH, extract with ether, dry (MgSO4), filter and remove the solvent in vacuo to obtain the product (2), [α]26D =+4.5° (c=5.0, ethanol). In an apparatus fitted with a Dean Stark trap Remove the solvent in vacuo dissolve the residue in 6.5 liters of methanol With cooling carefully add 125 g of NaBH4 and stir the mixture for 16 hours at room temperature Remove the methanol in vacuo add 2 liters water and 4 liters benzene extract the product into the benzene After drying (MgSO4) filter distill (b.p. 145°-150° C./0.5 mm) Wash the precipitate with a small amount of ice-cold ethanol recrystallize from 4.8 liters of ethanol wash with ice-cold ethanol filter off the solid product that from the original precipitation that from the recrystallization remove the solvent recover the free base extracting with benzene After drying (MgSO4) filtering removing the benzene to cool to room temperature Filter recrystallize once from 1.8 liter of ethanol followed by recrystallization from 4.0 liters of acetonitrile to obtain the desired R salt, m.p. 151°-152° C Basify with 400 ml of aqueous 2.5N NaOH, extract with ether dry (MgSO4) filter remove the solvent in vacuo

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

实验步骤: In an apparatus fitted with a Dean Stark trap, reflux a solution of 1.0 kg (6.75 mol) of benzylacetone, 725 g (6.75 mol) of benzylamine and 5.0 g of p-toluenesulfonic acid hydrate in 7 liters of benzene for 14 hours. Remove the solvent in vacuo, and dissolve the residue in 6.5 liters of methanol. With cooling and stirring, carefully add 125 g of NaBH4 and stir the mixture for 16 hours at room temperature. Remove the methanol in vacuo, and add 2 liters water and 4 liters benzene, and extract the product into the benzene. After drying (MgSO4), filter and distill (b.p. 145°-150° C./0.5 mm). Dissolve 1,028 g (4.288 mol) of the distillate and 1.23 kg (4.328 mol) of N-p-toluenesulfonyl-(L)-leucine in 7.2 liters of boiling ethanol and allow to cool to room temperature without agitation. Wash the precipitate with a small amount of ice-cold ethanol, recrystallize from 4.8 liters of ethanol, wash with ice-cold ethanol and filter off the solid product that is highly enriched with the salt of the undesired S enantiomer. Combine the mother liquor from the original precipitation and that from the recrystallization, remove the solvent and recover the free base by basifying with 500 ml of 20% aqueous NaOH and extracting with benzene. After drying (MgSO4), filtering and removing the benzene, dissolve the residue [487 g (2.04 mol)] and 346 g (2.06 mol) of N-acetyl-(L)-leucine in 2.0 liters of boiling ethanol and allow the solution to cool to room temperature. Filter and recrystallize once from 1.8 liter of ethanol followed by recrystallization from 4.0 liters of acetonitrile to obtain the desired R salt, m.p. 151°-152° C. Basify with 400 ml of aqueous 2.5N NaOH, extract with ether, dry (MgSO4), filter and remove the solvent in vacuo to obtain the product (2), [α]26D =+4.5° (c=5.0, ethanol). In an apparatus fitted with a Dean Stark trap Remove the solvent in vacuo dissolve the residue in 6.5 liters of methanol With cooling carefully add 125 g of NaBH4 and stir the mixture for 16 hours at room temperature Remove the methanol in vacuo add 2 liters water and 4 liters benzene extract the product into the benzene After drying (MgSO4) filter distill (b.p. 145°-150° C./0.5 mm) Wash the precipitate with a small amount of ice-cold ethanol recrystallize from 4.8 liters of ethanol wash with ice-cold ethanol filter off the solid product that from the original precipitation that from the recrystallization remove the solvent recover the free base extracting with benzene After drying (MgSO4) filtering removing the benzene to cool to room temperature Filter recrystallize once from 1.8 liter of ethanol followed by recrystallization from 4.0 liters of acetonitrile to obtain the desired R salt, m.p. 151°-152° C Basify with 400 ml of aqueous 2.5N NaOH, extract with ether dry (MgSO4) filter remove the solvent in vacuo

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

实验步骤: In an apparatus fitted with a Dean Stark trap, reflux a solution of 1.0 kg (6.75 mol) of benzylacetone, 725 g (6.75 mol) of benzylamine and 5.0 g of α-toluenesulfonic acid hydrate in 7 liters of benzene for 14 hours. Remove the solvent in vacuo, and dissolve the residue in 6.5 liters of methanol. With cooling and stirring, carefully add 125 g of NaBH4 and stir the mixture for 16 hours at room temperature. Remove the methanol in vacuo, and add 2 liters water and 4 liters benzene, and extract the product into the benzene. After drying (MgSO4), filter and distill (b.p. 145°-150° C./0.5 mm). Dissolve 1,028 g (4.288 mol) of the distillate and 1.23 kg (4.328 mol) of N-α-toluenesulfonyl-(L)-leucine in 7.2 liters of boiling ethanol and allow to cool to room temperature without agitation. Wash the precipitate with a small amount of ice-cold ethanol, recrystallize from 4.8 liters of ethanol, wash with ice-cold ethanol and filter off the solid product that is highly enriched with the salt of the undesired S enantiomer. Combine the mother liquor from the original precipitation and that from the recrystallization, remove the solvent and recover the free base by basifying with 500 ml of 20% aqueous NaOH and extracting with benzene. After drying (MgSO4), filtering and removing the benzene, dissolve the residue [487 g (2.04 mol)] and 346 g (2.06 mol) of N-acetyl-(L)-leucine in 2.0 liters of boiling ethanol and allow the solution to cool to room temperature. Filter and recrystallize once from 1.8 liter of ethanol followed by recrystallization from 4.0 liters of acetonitrile to obtain the desired R salt, m.p. 151°-152° C. Basify with 400 ml of aqueous 2.5N NaOH, extract with ether, dry (MgSO4), filter and remove the solvent in vacuo to obtain the product (2), [α]D26 =+4.5° (c=5.0, ethanol). In an apparatus fitted with a Dean Stark trap Remove the solvent in vacuo dissolve the residue in 6.5 liters of methanol With cooling carefully add 125 g of NaBH4 and stir the mixture for 16 hours at room temperature Remove the methanol in vacuo add 2 liters water and 4 liters benzene extract the product into the benzene After drying (MgSO4) filter distill (b.p. 145°-150° C./0.5 mm) Wash the precipitate with a small amount of ice-cold ethanol recrystallize from 4.8 liters of ethanol wash with ice-cold ethanol filter off the solid product that from the original precipitation that from the recrystallization remove the solvent recover the free base extracting with benzene After drying (MgSO4) filtering removing the benzene to cool to room temperature Filter recrystallize once from 1.8 liter of ethanol followed by recrystallization from 4.0 liters of acetonitrile to obtain the desired R salt, m.p. 151°-152° C Basify with 400 ml of aqueous 2.5N NaOH, extract with ether dry (MgSO4) filter remove the solvent in vacuo