Quinoline → HCID 86594125, compound

Participants

Reaction Conditions

Reaction Steps

Compounds of Formula I in which ring A is a quinoline can be prepared from a carbonyl-quinolin-1-one (XLM) via the method depicted in Scheme IXb. The carbonyl-quinolin-4-one (XLI) is converted to a triflate group by adding about 1.1 eq. to about 1.5 eq. trifluoromethanesulfonic anhydride (Tf2O) to a basic solution of the carbonyl-quinolin-1-one (XLIII) which is maintained at about 0° C. The reaction is complete in about 1 h to about 3 h to form a 1-trifluoromethanesulfonyloxy-carbonyl-quinoline (LXX). The triflate group can be reacted with a substituted phenylboronic acid (X) via the method depicted in Scheme I to form a (substituted phenyl)-carbonyl-quinoline (LXXI). The carbonyl group of the (substituted phenyl)-carbonyl-quinoline (LXXI) can be converted to an α,β-unsaturated carboxylic ester by adding the (substituted phenyl)-carbonyl-quinoline (LXXI) to a solution of 2-lithio-1,1-diflouroethene (prepared by combining an alkyl lithium with 1,1-difluoroethene at about −78° C.) while maintaining a temperature below −78° C. The resulting alcohol is isolated and immediately treated with methanol and H2SO4 to give a compound of Formula I in which ring A is a quinoline (LXXII).

Provenance & Evidence