Bromotrimethylsilane → HCID 178420877, compound

Participants

Reaction Steps

Example 1 describes preparation of 2-amino-9-[CR(-)-1-hydroxymethyl-3-diethylphosphono)-1-propyloxymethyl]- 9H-purine 1-5 as shown in Scheme 1. Briefly, the synthesis set forth in Scheme 1 involves, regiospecifically opening 2-(benzyloxymethyl) oxirane 1-1 with lithiated diethyl methylphosphonate in the presence of boron trifluoride etherate to afford 1-2 in 94% yield (Example 1, section (a.)). Compound 1-2 was then transformed to the corresponding chloromethyl ether and condensed with 2-amino-6-chloropurine in the presence of sodium hydride to give the nucleoside phosphonate 1-3 in 53% yield (Example 1, section (b.)). Treatment of 1-3 with 10% palladium/carbon and ammonium formate gave the 2-aminopurine phosphonate 1-4 in 66% yield (Example 1, section (c)). Finally, compound 1-4 was treated with excess bromotrimethylsilane to give the desired nucleoside phosphonate 1-5 in 35% yield (Example 1, section (d.)). Optical purity of compounds was determined by HPLC using a chiral column.

Provenance & Evidence