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Rapid Optimization of the Hydrolysis of N ‘-Trifluoroacetyl- S - tert -leucine- N -methylamide Using High-Throughput Chemical Development Techniques

2001; American Chemical Society; Volume: 5; Issue: 3 Linguagem: Inglês

10.1021/op010011s

1520-586X

Victor W. Rosso, James L. Pazdan, John J. Venit,

Scientific Computing and Data Management

Our efforts are focused on the application of automation to Process R&D. This article will describe the application of high throughput methods to rapidly investigate a development challenge. In this case we needed to study the deprotection of N'-trifluoroacetyl-S-tert-leucine-N-methylamide which afforded a lower than expected yield when subjected to standard deprotection reaction conditions. This chemistry was systematically investigated by a sequential series of high-throughput experiments using various automated and semi-automated systems. The studies included a combinatorial screen of discrete reaction conditions, a screening DOE to study a broad range of continuous factors, and a two-factor central composite design to optimize the important factors. By applying high-throughput methods we were able to optimize the yield of the reaction by performing a large number of experiments in a short period of time.