Ammonia → HCID 20280761, compound

Participants

Reaction Steps

Birch reduction with lithium or sodium in liquid ammonia of 85 mmol of unpurified 7 with 1.92 g atom of lithium in 450 ml of liquid NH3, 225 ml each of dry THF and 6-BuOH at -55° to -65° C. for 4 hrs., then at -75° C. until no 7 remained by TLC (~1.5 h) afforded (90%) essentially pure (TLC) 8, mp 179.5° C. Refluxing unpurified 8 with 1.5 equivalents of pure PhOCHO, chloral in 10 volumes of EtOAc or in EtOCHO until TLC showed absence of 8 gave (94%) pure 10, which, as the N-formyl derivatives described below and others, existed as two distinct rotomers, as shown by NMR. This N-formyl derivatization introduces a protective group for the nitrogen in the subsequent steps of the reaction. Compound 7 or 8 may be N-methylated with methyl halide or sulfonate to give compound 9. Stirring a solution of 10 (25° C., 1 h.) in 20 volumes of dry THF containing 1% (v/v) CH3SO3H and 3 molar equivalents of ethylene glycol generated a solution of ketal 11 (quantitatively by TLC) which was treated at 0°-5° C. during 0.5 h with 1.05 equivalents of recrystallized N-bromoacetamide (NBA) to afford essentially pure bromoketal 12 after neutralization with NH3 gas, solvent evaporation and workup with CHCl3 --H2O. Bromoketal 12 was most efficiently deketalized in 6 volumes of 5:1 88% HCO2H--H2O (25° C., 1 h) followed by CHCl3 -aqueous NaHCO3 workup to afford 13, IR (CHCl3) 1717 (C=O) and 1665 (NCHO) cm-1 in 90% yield from 10.

Provenance & Evidence