Patent
Process for the preparation of 5-cyanophthalide starting from 5-carboxyphthalide
| العنوان: | Process for the preparation of 5-cyanophthalide starting from 5-carboxyphthalide |
|---|---|
| Patent Number: | 7,482,476 |
| تاريخ النشر: | January 27, 2009 |
| Appl. No: | 11/581133 |
| Application Filed: | October 13, 2006 |
| مستخلص: | A new process is described for obtaining 5-cyanophthalide, which is an intermediate used for the synthesis of citalopram and its active enantiomer S(+) citalopram, both of which are known active ingredients commonly used for treating depression. The process involves starting from 5-carboxyphthalide which is converted into the corresponding acylochloride. The latter is reacted with hydroxylamine to produce the corresponding hydroxamyl phthalide, which is subsequently subjected to a dehydration reaction to produce 5-cyanophthalide. |
| Inventors: | Cotticelli, Giovanni (Milan, IT); Salvetti, Raul (Malonno, IT); Zappa, Marco (Abbiategrasso, IT) |
| Assignees: | Adorkem Technology SpA (S. Costa Volpino (Bergamo), IT) |
| Claim: | 1. A process for the production of 5-cyanophthalide comprising: (a) converting 5-carboxyphthalide into 5-halocarbonyl phthalide by reacting 5-carboxyphthalide with thionyl chloride; (b) converting the 5-halocarbonyl phthalide into5-phthalide-(N-hydroxycarboxamide), and; (c) dehydrating the 5-phthalide-(N-hydroxycarboxamide) with thionyl chloride. |
| Claim: | 2. A process according to claim 1 , wherein step (a) comprises converting in the presence of an aprotic, polar, organic solvent. |
| Claim: | 3. A process according to claim 2 , wherein step (a) comprises converting at reflux temperature. |
| Claim: | 4. A process according to claim 2 , wherein the aprotic, polar, organic solvent comprises a solvent selected from the group consisting of DMF and/or DMSO. |
| Claim: | 5. A process according to claim 1 , wherein the 5-halocarbonyl phthalide is not isolated or purified. |
| Claim: | 6. A process according to claim 1 , wherein step (b) further comprises reacting the 5-halocarbonyl phthalide with hydroxylamine. |
| Claim: | 7. A process according to claim 1 , wherein step (b) comprises converting in an aprotic organic solvent. |
| Claim: | 8. A process according to claim 7 , wherein the organic solvent is selected from THF and/or toluene. |
| Claim: | 9. A process according to claim 1 . wherein step (b) comprises converting at a temperature of from 0 to +20° C. |
| Claim: | 10. A process according to claim 1 , wherein step (b) comprises converting at a temperature of from +5 to +15° C. |
| Claim: | 11. A process according to claim 1 , wherein the dehydrating agent is used as a reaction solvent. |
| Claim: | 12. A process according to claim 11 , wherein step (c) comprises dehydrating at the reflux temperature of the solvent. |
| Current U.S. Class: | 549/467 |
| Patent References Cited: | 6441201 August 2002 Weber WO 00/39112 July 2000 |
| Other References: | Liguori et al., Synthesis, 2:168 (1987). cited by other |
| Assistant Examiner: | Chandrakumar, Nizal S |
| Primary Examiner: | Seaman, D. Margaret |
| Attorney, Agent or Firm: | Perkins Coie LLP |
| رقم الانضمام: | edspgr.07482476 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |