Nitromethane → 3-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-4-nitro-butyric acid ethyl ester
Reaktionsgleichung
[CH2:1]([O:3][C:4](=[O:14])[CH:5]=[CH:6][CH:7]1[CH2:11][O:10][C:9]([CH3:13])([CH3:12])[O:8]1)[CH3:2].[N+:15]([CH3:18])([O-:17])=[O:16]>>[CH2:1]([O:3][C:4](=[O:14])[CH2:5][CH:6]([CH:7]1[CH2:11][O:10][C:9]([CH3:13])([CH3:12])[O:8]1)[CH2:18][N+:15]([O-:17])=[O:16])[CH3:2]Komponenten
3
Versuchsvorschrift
WO03/022853 in Example I provides a Wittig route which employs triethyl phosphono acetate (TEPA) to obtain 3-(2,2-dimethyl-[1,3]dioxolan-4-yl)-acrylic acid ethyl ester. The subsequent Michael addition to 3-(2,2-dimethyl-[1,3]dioxolan-4-yl)-acrylic acid ethyl ester, presents limitations in that it produces a nitromethane adduct, i.e. 3-(2,2-dimethyl-[1,3]dioxolan-4-yl)-4-nitro-butyric acid ethyl ester, with a syn:anti ratio of approximately 8:2. Subsequent reduction followed by Nef/cyclization reactions yields the (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol seriously contaminated with its exo-diastereoisomer, i.e. (3R,3aR,6aS) hexahydro-furo[2,3-b]furan-3-ol, with a ratio endo:exo of around 8:2. Although this process does not possess several of the disadvantages attached to the Knoevenagel process, it does not produce pure endo-diastereoisomer since there is no purification step available, such as crystallization, to remove the undesired exo-diastereoisomers that have been formed during the Michael addition in the anti configuration.