4-Fluoroaniline → N-(4-Fluorophenyl)-2,5-anhydro-2,5-imino-D-glucitol

Participants

Reaction Steps

A solution of 4-fluoroaniline (30 g, 0.27 mol) and 15.46 mL of HOAC in 100 mL of MEOH was added to 5-keto-D-fructose (57.7 g, 0.324 mol) in 350 mL of MEOH. To this suspension was added 32 g of NaCNBH3 (0.5 mol). The tan mixture was heated at reflux. After reacting overnight, the solution was cooled, the MeOH was largely evaporated and the residue was dissolved in ca. 200 ml. of water and treated with ca. 500 mL of Dowex 50W-X8 cation exchange resin. After stirring for 2 h, the resin and solution were added to a column with a bed of 150 mL more resin, and the supernatant was eluted. The resin was then washed with another ca. 500 mL of water. The column was then eluted with 1N NH4OH, and the water of the fractions containing the products was removed under reduced pressure. The residue was purified on two Waters Prep 500.HPLC columns (hexane/iPrOH/NH4OH, 65:34:1) to give fractions highly enriched in all three stereoisomers. The fastest eluting material was recrystallized from iPrOH/hexane to give 4.9 g white needles (7%) of the mannitol isomer (Formula XVII). Both C-13 and H-1 NMR are consistent with the assigned structure. M.p. 198° C. (browning), 205°-207° C.; (melting with decomposition).

Provenance & Evidence