Formic Acid → methyl (Z)-(2S,3S,4R)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoate

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Reaction Conditions

Reaction Steps

To a solution of 12.97 g (0.0425 mol) of methyl (Z)-(2S,3S,4S)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoate, 26.57 g (0.101 mol) of triphenylphosphine and 3.32 g (2.72 mL, 0.069 mol) of 95% formic acid in 130 ml of tetrahydrofurane is added dropwise with stirring under argon at 10° C. 17.63 g (15.94 ml, 0.101 mol) of diethyl azodicarboxylate over a period of 10 min. The mixture is stirred at room temperature for one h and evaporated. The residue is triturated with ether and the mixture is allowed to stand at 0° C. overnight. The precipitated triphenylphosphine oxide is filtered and washed with ether. The combined filtrates and washings axe evaporated to dryness. The residue is dissolved in 130 ml of methanol and hydrogen chloride gas is bubbled through the solution for 3 to 5 min. The mixture is stirred for 30 min and evaporated to dryness. The residue is dissolved in 56 ml of water and the solution is extracted with ethyl acetate (3×). The aqueous layer is mixed with 100 ml of methylene chloride and neutralized with solid sodium bicarbonate with vigorous stirring. The layers are separated and the aqueous layer is extracted with methylene chloride (3×). The combined methylene chloride extracts are washed with brine, dried (MgSO4) and evaporated to give 12.68 g of methyl (Z)-(2S,3S,4R)-7-[4-hydroxy-2-(3-pyridyl)-tetrahydrofuran-3-yl]-4-heptenoate as oil with elemental analysis: C,66.1; H,7.36; N,4.89 (theory: C,66.86; H,7.59; N,4.59) and mass spectrum m/z 306 (M+1) (Calcd. MW=305.38).

Provenance & Evidence