Benzyloxycarbonyl-L-phenylalanine → Dibenzyl ether

Participants

Reaction Steps

Boc-Phe 7 is converted to the allylic alcohol 8 using the same procedures reported by De Lucca et al. for the conversion of Z-Phe to the corresponding Z-allylic alcohol (J. Med. Chem. 1997, 40, 1707-1719). The allylic alcohol 8 is reacted with 4-methoxybenzylmagnesium chloride to afford the alkene 9 (J. Med. Chem. 1997, 40, 1707-1719). The 4-methoxybenzylmagnesium chloride is prepared from 4-methoxybenzylchloride according to the procedure of Van Campen et al. (J. Amer. Chem. Soc. 1948, 70 p2296). The alkene 9 is converted to the tetrahydropyrimidinone 10 using the same series of procedures reported by De Lucca et al. (J. Med. Chem. 1997, 40, 1707-1719). Treatment of the nitrile 10 with hydrogen peroxide in DMSO affords the carboxamide 11 (Synthesis, 1989, 949-950). The carboxamide 11 is treated with trimethylsilylbromide to form the phenol 12 (Green) which is then alkylated with trifluoro-methanesulfonic acid bis-benzyloxy-phosphorylmethyl ester in the presence of base (e.g. cesium carbonate) to yield the dibenzyl phosphonate 13.

Provenance & Evidence