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As State Secretary of the Parteikanzlerei (Party Chancellery), Klopfer represented Bormann, who was head of the Parteikanzlei, at the Wannsee Conference on 20 January 1942 in which the details of the "Final Solution of the Jewish Question" were formalised, policies that culminated in the Holocaust. Along with Helmuth Friedrichs Klopfer was the highest-ranking bureaucrat behind Bormann in the Chancellery. This position gave him extensive power of patronage within the Nazi Party as Bormann often left appointments to party positions to Klopfer and Friedrichs.
As the Red Army closed in on Berlin in 1945, Klopfer fled the city. He was captured and imprisoned and was charged with war crimes but was released for lack of evidence. He became a tax advisor in the city of Ulm (Baden-Württemberg). He was the last surviving attendee of the Wannsee Conference, dying in 1987.