Free energy changes associated with chemical reactions in solution are treated by integral equation theory in the form of the 3D reference interaction site model (RISM) in combination with quantum-chemical calculations via an embedded cluster approach (EC-RISM). The electronic structure of the solute is computed self-consistently with the solvent structure by mapping the charge distribution of the solvent onto a set of discrete background point charges that are added to the molecular Hamiltonian. The EC-RISM procedure yields chemical accuracy in free energy predictions for several benchmark systems without adjusting empirical parameters. We apply the method to the standard reaction free energy for the gauche-trans equilibrium of 1,2-dichloroethane in water and to pKa shift calculations for trifluoroacetic acid/acetic acid and 4-nitroaniline/aniline in water.