The process development of a dimethyltitanocene-mediated ester olefination is described. The synthetic challenges and stability issues involving large-scale production of dimethyltitanocene are documented, and the optimization of the ester olefination is detailed. The process described was used to make hundreds of kilograms of an advanced intermediate for aprepitant (Emend).
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Payack et al. (2004) studied this question.
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