(3aR,7aS)-2-benzyl-1,3,3a,6,7,7a-hexahydropyrano[3,4-c]pyrrol-4-one

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (±) cis-2-benzyl-hexahydropyrano[3,4-c]pyrrole-4(1H)-one (D20) (180 g, 0.78 mole) in ethanol (400 ml) was stirred and cooled to 0° C. and hydrogen bromide gas introduced at such a rate that the temperature did not rise above 20° C. until the solution was saturated. The reaction was allowed to stand at room temperature for 6 h. The reaction was then poured into a well stirred mixture of chloroform (2 L) and saturated aqueous potassium carbonate solution (1.5 L) which was cooled by the addition of solid carbon dioxide. The organic layer was separated and the aqueous layer extracted with chloroform (4×1 L). The combined organic extracts were dried (Na2SO4) concentrated in vacuo to a gum. The gum was then stirred with ether (3×750ml) to remove any unreacted starting material and the ether insoluble gum dissolved in ethanol (1 L). Palladium on charcoal 10% (20 g) was then added and the mixture stirred under an atmosphere of hydrogen at 50° C. for 6 h when the uptake of hydrogen was complete. The reaction was then filtered through Kieselguhr and concentrated in vacuo to a gum. This was partitioned between chloroform and saturated aqueous potassium carbonate solution. The organic phase was separated, dried over sodium sulphate and concentrated in vacuo to a gum. Distillation in vacuo afforded the title compound (D21, 75 g, 0.44 mole, 56%) as an oil b.p. 90°-95° C.0.5mmHg did not rise above 20° C. until the solution The reaction was then poured into a well The organic layer was separated the aqueous layer extracted with chloroform (4×1 L) The combined organic extracts were dried (Na2SO4) concentrated in vacuo to a gum The gum was then stirred with ether (3×750ml) to remove the ether insoluble gum dissolved in ethanol (1 L) Palladium on charcoal 10% (20 g) was then added the mixture stirred under an atmosphere of hydrogen at 50° C. for 6 h when the uptake of hydrogen The reaction was then filtered through Kieselguhr concentrated in vacuo to a gum This was partitioned between chloroform and saturated aqueous potassium carbonate solution The organic phase was separated dried over sodium sulphate concentrated in vacuo to a gum Distillation in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 5,6-dihydro-2H-pyran-2-one* (136 g, 1.39 mole) in dichloromethane (2 L) at -20° C. was added N-benzyl-N-(methoxymethyl)-N-trimethylsilylmethyl amine (80% pure) (D12, 450 g, 1.5 mole). To this solution was added trifluoroacetic acid in dichloromethane (140 ml, 1 molar solution) at -20° C. The reaction was then transferred at -20° C. under a small positive pressure of nitrogen via a double ended needle to a second flask on a water bath at 30° C. As the cold mixture warmed up an exothermic reaction occurred and the rate of addition was controlled to maintain gentle reflux. When addition was complete and the reaction had subsided the solution was allowed to stand at room temperature for 2 h. The reaction was then washed with saturated aqueous potassium carbonate solution, dried (Na2SO4) and concentrated in vacuo to a gum. Vacuum distillation afforded the title compound as a single main fraction b.p. 180°-190° C. 0.5mmHg (D20, 180.9 g, 0.73 mole, 56%). was then transferred at -20° C. under a small positive pressure of nitrogen at 30° C As the cold mixture warmed up an exothermic reaction the rate of addition to maintain gentle reflux When addition The reaction was then washed with saturated aqueous potassium carbonate solution dried (Na2SO4) concentrated in vacuo to a gum Vacuum distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 5,6-dihydro-2H-pyran-2-one* (136 g, 1.39 mole) in dichloromethane (2 L) at -20° C. was added N-benzyl-N-(methoxymethyl)-N-trimethylsilylmethyl amine (80% pure) (D12, 450 g, 1.5 mole). To this solution was added trifluoroacetic acid in dichloromethane (140 ml, 1 molar solution) at -20° C. The reaction was then transferred at -20° C. under a small positive pressure of nitrogen via a double ended needle to a second flask on a water bath at 30° C. As the cold mixture warmed up an exothermic reaction occurred and the rate of addition was controlled to maintain gentle reflux. When addition was complete and the reaction had subsided the solution was allowed to stand at room temperature for 2 h. The reaction was then washed with saturated aqueous potassium carbonate solution, dried (Na2SO4) and concentrated in vacuo to a gum. Vacuum distillation afforded the title compound as a single main fraction b.p. 180°-190° C.0.5mmHg (D20, 180.9 g, 0.73 mole, 56%). was then transferred at -20° C. under a small positive pressure of nitrogen at 30° C As the cold mixture warmed up an exothermic reaction the rate of addition to maintain gentle reflux When addition The reaction was then washed with saturated aqueous potassium carbonate solution dried (Na2SO4) concentrated in vacuo to a gum Vacuum distillation