2-(2,6-dimethoxyphenoxy)acetaldehyde

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

Procedure: A mixture of 4.5 g of Intermediate XII, 3.7 g of triphenyl phosphine and 2.85 g of 2,6-dimethoxyphenoxy-acetaldehyde (prepared as per Nelson, W. L. et al., J. Med. Chem. 22: 1125, 1979) in 45 ml of benzene was stirred at 20°-25° C. for 18 hours and at reflux for 5 hours. The solvent was evaporated off in vacuo and the residue was dissolved in 80 ml of anhydrous methanol containing 3Å molecular sieves at 0° C. The mixture was stood for 1 hour at 0° C. and for 1 hour at 20°-25° C., and then poured into iced water and extracted with dichloromethane. The organic extracts were washed with water and dried on anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by flash chromatography on silica gel, eluting with dichloromethane:methanol (49:1). The base obtained was treated with ethanolic hydrogen chloride. After crystallization from ethanol, the title compound was obtained. Yield 40%, m.p. 200-°202° C. at reflux for 5 hours The solvent was evaporated off in vacuo the residue was dissolved in 80 ml of anhydrous methanol containing 3Å molecular sieves at 0° C The mixture was stood for 1 hour at 0° C. and for 1 hour at 20°-25° C. poured into iced water extracted with dichloromethane The organic extracts were washed with water dried on anhydrous sodium sulfate The solvent was removed in vacuo the residue was purified by flash chromatography on silica gel eluting with dichloromethane:methanol (49:1) The base obtained After crystallization from ethanol

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

Procedure: A mixture of 4.5 g of Intermediate XII, 3.7 g of triphenyl phosphine and 2.85 g of 2,6-dimethoxyphenoxy-acetaldehyde (prepared as per Nelson, W. L. et al., J. Med. Chem. 22: 1125, 1979) in 45 ml of benzene was stirred at 20°-25° C. for 18 hours and at reflux for 5 hours. The solvent was evaporated off in vacuo and the residue was dissolved in 80 ml of anhydrous methanol containing 3Å molecular sieves at 0° C. The mixture was stood for 1 hour at 0° C. and for 1 hour at 20°-25° C., and then poured into iced water and extracted with dichloromethane. The organic extracts were washed with water and dried on anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by flash chromatography on silica gel, eluting with dichloromethane:methanol (49:1). The base obtained was treated with ethanolic hydrogen chloride. After crystallization from ethanol, the title compound was obtained. Yield 40%, m.p. 200-°202° C. at reflux for 5 hours The solvent was evaporated off in vacuo the residue was dissolved in 80 ml of anhydrous methanol containing 3Å molecular sieves at 0° C The mixture was stood for 1 hour at 0° C. and for 1 hour at 20°-25° C. poured into iced water extracted with dichloromethane The organic extracts were washed with water dried on anhydrous sodium sulfate The solvent was removed in vacuo the residue was purified by flash chromatography on silica gel eluting with dichloromethane:methanol (49:1) The base obtained After crystallization from ethanol

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

Procedure: A mixture of 4.5 g of Intermediate XII, 3.7 g of triphenyl phosphine and 2.85 g of 2,6-dimethoxyphenoxy-acetaldehyde (prepared as per Nelson, W. L. et al., J. Med. Chem. 22: 1125, 1979) in 45 ml of benzene was stirred at 20°-25° C. for 18 hours and at reflux for 5 hours. The solvent was evaporated off in vacuo and the residue was dissolved in 80 ml of anhydrous methanol containing 3Å molecular sieves at 0° C. The mixture was stood for 1 hour at 0° C. and for 1 hour at 20°-25° C., and then poured into iced water and extracted with dichloromethane. The organic extracts were washed with water and dried on anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by flash chromatography on silica gel, eluting with dichloromethane: methanol (49:1). The base obtained was treated with ethanolic hydrogen chloride. After crystallization from ethanol, the title compound was obtained. Yield 40%, m.p. 200°-202° C. at reflux for 5 hours The solvent was evaporated off in vacuo the residue was dissolved in 80 ml of anhydrous methanol containing 3Å molecular sieves at 0° C The mixture was stood for 1 hour at 0° C. and for 1 hour at 20°-25° C. poured into iced water extracted with dichloromethane The organic extracts were washed with water dried on anhydrous sodium sulfate The solvent was removed in vacuo the residue was purified by flash chromatography on silica gel eluting with dichloromethane: methanol (49:1) The base obtained After crystallization from ethanol