2-amino-1,2-diphenylethanone;hydrochloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al, Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshly distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added, and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH~2) was added dropwise. The mixture was heated at reflux another hour, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution. With stirring, more sodium bicarbonate was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al, J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was heated at reflux for two hours heating at reflux The mixture was heated at reflux another hour The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al, Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshly distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added, and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH~2) was added dropwise. The mixture was heated at reflux another hour, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution. With stirring, more sodium bicarbonate was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al, J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was heated at reflux for two hours heating at reflux The mixture was heated at reflux another hour The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al, Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshly distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH~2) was added dropwise. The mixture was heated at reflux another hour, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution. With stirring, more sodium bicarbonate was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al, J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was heated at reflux for two hours heating at reflux The mixture was heated at reflux another hour The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al, Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshly distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH~2) was added dropwise. The mixture was heated at reflux another hour, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution. With stirring, more sodium bicarbonate was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al, J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was heated at reflux for two hours heating at reflux The mixture was heated at reflux another hour The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al., Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshyl distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was then heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added, and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH ~2) was added dropwise. The mixture was heated at reflux another hours, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution, With stirring, more sodium bicarbonate was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al., J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was then heated at reflux for two hours heating at reflux The mixture was heated at reflux another hours The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al., Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshyl distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was then heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added, and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH ~2) was added dropwise. The mixture was heated at reflux another hours, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution, With stirring, more sodium bicarbonate was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al., J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was then heated at reflux for two hours heating at reflux The mixture was heated at reflux another hours The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al., Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshyl distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was then heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added, and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH ~2) was added dropwise. The mixture was heated at reflux another hours, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution, With stirring, more sodium bicarbonate was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al., J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was then heated at reflux for two hours heating at reflux The mixture was heated at reflux another hours The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9 g of 7-cyanooctanoic acid dicyclohexylamine salt is added to a mixture of 28 cm3 of a molar solution of sodium hydrogen sulphate and 60 cm3 of diethyl ether. The mixture is stirred for 15 minutes at 20° C. and the organic phase is then separated. The latter is dried over magnesium sulphate and filtered and the solvent is evaporated off under reduced pressure. The residue is treated with 14.8 g of thionyl chloride and heated to 50° C. for 3 hours. The mixture is concentrated under reduced pressure. The residual oil is dissolved in 6 cm3 of dichloromethane, and the solution obtained is added to a suspension, stirred and cooled to 5° C. of 6 g of 2-amino-1,2-diphenylethanone hydrochloride in 30 cm3 of dichloromethane containing 4.8 g of pyridine. After treatment, the product obtained is chromatographed on a column 2 cm in diameter containing 48 g of silica gel (50 to 200μ). The column is eluted, collecting 100 cm3 fractions, with 1.2 liters of a diisopropyl ether/ethyl acetate (80:20 by volume) mixture. The fractions emerging at between 0.3 and 1.2 liters are concentrated under reduced pressure (0.2 kPa). 5.9 g (67%) of (RS) -1,2-diphenyl-2-(7-cyanooctanamido)ethanone are obtained in the form of an oil, which is used directly in the subsequent reaction. the organic phase is then separated The latter is dried over magnesium sulphate filtered the solvent is evaporated off under reduced pressure The residue is treated with 14.8 g of thionyl chloride heated to 50° C. for 3 hours The mixture is concentrated under reduced pressure The residual oil is dissolved in 6 cm3 of dichloromethane the solution obtained is added to a suspension stirred After treatment, the product obtained is chromatographed on a column 2 cm in diameter containing 48 g of silica gel (50 to 200μ) The column is eluted collecting 100 cm3 fractions are concentrated under reduced pressure (0.2 kPa)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed 76.7 g (0.31 mole) of desyl amine hydrochloride [Pschorr et al, Chem. Ber., 35, 2740 (1902)], 750 ml methanol, 88 g (0.62 mole) dimethyl acetylenedicarboxylate (freshly distilled) and 61 g (0.75 mole) anhydrous sodium acetate. The mixture was heated at reflux for two hours. Then another 44 g (0.31 mole) of dimethyl acetylenedicarboxylate was added, and heating continued another two hours. While the reaction mixture was still at reflux, concentrated hydrochloric acid (~60 ml, to pH~2) was added dropwise. The mixture was heated at reflux another hour, then poured into 2 l water containing 200 ml 10% sodium bicarbonate solution. With stirring, more sodium bicarbonte was added until the solution was neutral. The gummy solid which precipitated was collected and washed with water. Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol to give 65.5 g (63%) of white crystals, m.p. 191°-2° [Lit. m.p. 185°-7°; J. B. Hendrickson et al, J. Am. Chem. Soc., 86, 107 (1964)]. In a 2 l RB 3-neck flask with mechanical stirrer and condenser was placed The mixture was heated at reflux for two hours heating at reflux The mixture was heated at reflux another hour The gummy solid which precipitated was collected washed with water Trituration of this gummy material with ~500 ml of 50% aqueous ethanol gave a tan powdery solid, which was recrystallized from ~85% aqueous ethanol