| Autor: |
Bogaert-Alvarez, R. J., Demena, P., Kodersha, G., Polomski, R. E., Soundararajan, N., Wang, S. S. Y. |
| Zdroj: |
Organic Process Research & Development; November 2001, Vol. 5 Issue: 6 p636-645, 10p |
| Abstrakt: |
The thermal Claisen rearrangement of 4-cyanophenyl 1,1-dimethylpropargyl ether (4) to 6-cyano-2,2-dimethylchromene (5), (6-cyano-2,2-dimethyl-2H-1-benzopyran), which is used in the synthesis of a potassium channel activator drug candidate, BMS-180448, created a significant process development issue. The resulting large heat release in this conversion posed not only a safety risk but could also cause product degradation if done in a batch-wise manner. The solution was to exploit the high surface-to-volume ratio of a plug-flow reactor that would maximize the heat transfer, thereby permitting tight and responsive temperature with better reaction control. In the course of successfully testing the plug-flow concept on micro-flow scale (gram quantity) and kilo-flow scale (~10 kg), a generalized mathematical model capable of predicting the reaction performance based on the physical properties of any given plug-flow reactor was generated. The model provides requisite information to design and operate a plug-flow reactor of any size for this reaction. This model would optimize reaction conditions for an acquired reactor system capable of producing ~7 kg/h of the dimethylchromene. Application of plug-flow reactor technology enabled production of high quality 2,2-dimethylchromenes in good yield (>98 mol %) without the use of solvents and with virtually no waste streams. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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