反应详情

A solution of 0.971 g (4.18 mmol) of (7R,8aS)-7-hydroxy-2-phenylmethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Diafi, L.; et al. J. Het. Chem., 1990, 27, 2181), 0.703 g (6.27 mmol) of 4-fluorophenol and 1.32 g (5.02 mmol) of triphenylphosphine in 20 mL of dry THF was treated with 0.79 mL (5.02 mmol) of diethyl azodicarboxylate and the solution stirred at room temperature for 21 h. Excess HCl (g) in diethyl ether was added, the precipitate was collected on a Buchner funnel, washing with ethyl acetate. The gummy residue was dissolved in a mixture of ethyl acetate and aqueous ammonium hydroxide, the layers were separated, the aqueous phase was extracted with more ethyl acetate (2×), the combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by silica gel MPLC with 95:5 ethyl acetate:methanol gave 1.3 g (95%) of (7S,8aS)-7-(4-fluorophenoxy)-2-phenylmethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine.

1. customthe precipitate was collected on a Buchner funnel
2. washwashing with ethyl acetate
3. dissolutionThe gummy residue was dissolved in a mixture of ethyl acetate and aqueous ammonium hydroxide
4. customthe layers were separated
5. extractionthe aqueous phase was extracted with more ethyl acetate (2×)
6. dry with materialthe combined organic phase was dried (magnesium sulfate)
7. filtrationfiltered
8. customevaporated
9. customPurification by silica gel MPLC with 95:5 ethyl acetate