Preparation of 3-ethynylaniline

3-Ethynylaniline is the building block from which the ethynylphenylamino group of erlotinib, a lung-cancer drug, is derived. Small terminal alkynes such as acetylene are gases that are difficult to handle, and protected equivalents are used instead.

2-Methylbut-3-yn-2-ol, a cheap liquid made from acetone and acetylene, is coupled with 3-bromoaniline by the Sonogashira reaction. On heating the product with NaOH, the addition of acetone to the acetylide is reversed (a retro-Favorskii reaction) and the terminal alkyne is released.