In 1920, Duruflé entered the Conservatoire de Paris. Duruflé left the Conservatoire with first prizes in organ, harmony, piano accompaniment, and composition. In 1927, Louis Vierne nominated him as his assistant at Notre Dame. Duruflé became titular organist of St. Etienne-du-Mont in Paris in 1930, a position he held throughout his life.
In 1939, he premiered Francis Poulenc's Organ Concerto (the Concerto for Organ, Strings and Timpani in G minor). Duruflé had advised Poulenc on the registrations of the organ part. In 1943 he became professor of harmony at the Conservatoire de Paris, where he worked until 1970. In 1947, Duruflé wrote what is probably the most famous of his very few pieces: the Requiem op.
9, for soloists, choir, organ and orchestra. The same year, Marie-Madeleine Chevalier became his assistant at St-Etienne-du-Mont. Duruflé married her in 1953. A car accident in 1975 inflicted severe injuries upon Duruflé, and after it he gave up performing; indeed he was largely confined to his apartment. He died in Paris in 1986, aged 84.
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