Propyl iodide, 2-methoxy-3-

We turned our efforts to a synthesis in which a chiral 5-carbon unit would be coupled to a 6-carbon structure bearing functionality permitting resolution. The 5-carbon fragment would contain the hydrocarbon asymmetric center (C-8 of VII) the other unit would provide C-2. Commercially available (S>)-2-methyl 1-butanol was determined to be >99% pure. However, the R-alcohol (acid, aldehyde, etc.) would have to be synthesized. Asymmetric alkylations of chiral a-metallated amides were performed, but the enantiomeric excesses were not sufficiently high. In particular we noted that alkylations involving a short chain bifunctional compound (e.g., 3-methoxy-propyl iodide) provided slightly lower ee s than did the parent alkyl iodide. 

Two of the compounds described here are 4-alkoxy homologs of mescaline. These have been prepared by the appropriate alkylation of syringaldehyde with either ethyl or propyl iodide followed by the formation of a nitrostyrene with nitromethane. These intermediates were then reduced with LAH to form the product amines 4-ethoxy-3,5-dimethoxyphenethylamine (1) and 4-propoxy-3,5-diimethoxy-phenethylamine (2), respectively. These products have been called escaline and proscaline in keeping with the well-established trivial name mescaline for the 4-methoxy counterpart. These reactions are shown in scheme I. 

To a solution of 4 g of sodium in 200 ml of n-propanol is added 39 g of homovanillic acid-n-propyl ester (boiling point 160°C to 162°C/4 mm Hg) and the mixture is concentrated by evaporation under vacuum. After dissolving the residue in 200 ml of dimethylformamide and the addition of 0.5 gof sodium iodide, 26.2 g of chloracetic acid-N,N-diethylamide are added drop-wise with stirring at an internal temperature of 130°C, and the mixture is further heated at 130°C for three hours. From the cooled reaction mixture the precipitated salts are removed by filtering off with suction. After driving off the dimethylformamide under vacuum, the product is fractionated under vacuum, and 44.3 g of 3-methoxy-4-N,N-diethylcarbamido-methoxy phenyl acetic acid-n-propyl ester are obtained as a yellowish oil of boiling point 210°C to 212°C/0,7 mm Hg,... 

COCH3 - Preparation by adding 2-hydroxy-3-iodo-6-methoxy-acetophenone and cuprous iodide to a solution of OCH3 sodium propoxide, previously prepared from propyl... 

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