• Home
  • Search Results
  • Preparation of a fludarabine intermediate via selective alkylation of 2-fluoroadenine.

Preparation of a fludarabine intermediate via selective alkylation of 2-fluoroadenine.

Nucleosides, nucleotides & nucleic acids (2006-08-11)
Brian E Schulmeier, William R Cantrell, William E Bauta
ABSTRACT

The reaction between 2-fluoroadenine (3) and 1,3,5-tri-O-benzyl-1-alpha-D-chloroarabinofuranose (4) with potassium t-amylate was evaluated in various solvents to afford 9-beta-D-(2,3,5-tri-O-benzyl-arabinofuranosyl)-2-fluoroadenine (5) and the corresponding alpha-anomer (6). In addition, 7-beta-D-(2,3,5-tri-O-benzyl-arabinofuranosyl)-2-fluoroadenine (7) and an unusual "bis-fluoroadenine" nucleoside (8) were isolated as byproducts. The highest anomeric ratio (beta/alpha > 10) and conversion (> 80%) were observed with the highly polar solvent sulfolane. This reaction was demonstrated on gram scale as a practical laboratory synthesis of 5, a known intermediate in the synthesis of fludarabine.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-Methyl-2-butanol, ReagentPlus®, 99%
Sigma-Aldrich
2-Methyl-2-butanol, ReagentPlus®, ≥99%
Sigma-Aldrich
2-Methyl-2-butanol, anhydrous, ≥99%
Supelco
2-Methyl-2-butanol, analytical standard
Sigma-Aldrich
2-Fluoroadenine, 96%