Continuous celecoxib preparation

Many continuous processes are used to prepare early pharmaceutical intermediates, but Pfizer recently presented a continuous process to prepare the API itself. A continuous process to prepare the anti-inflammatory drug celecoxib was described (Scheme 11.3) [6]. The batch process for celecoxib consists of two steps (1) a base-mediated Claisen reaction between 4-methylacetophenone and ethyl trifluoroacetate, and (2) an acid-mediated pyrazole condensation between enolate intermediate 8 and hydrazine 9 giving celecoxib (Scheme 11.4) [7]. Continuously flowing the Claisen reaction step 1 into the pyrazole condensation step 2 offers the advantages of directly telescoping continuous processing steps, as described in the introduction to this chapter. 

Scheme 11.3 Telescoped continuous process for the preparation of celecoxib.

Figure 11.5 Pilot plant scale continuous process for the preparation of celecoxib. The step 1 reactor with a 0.41-inch ID residence time section is shown.

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