- Preparation method for nefopam hydrochloride
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The invention discloses a preparation method for nefopam hydrochloride. The preparation method is characterized by comprising the following preparation steps: (A) performing a reaction on raw materials including tert-butyl N-benzyl-N-methyl carbamate and benzoyl chloride to obtain an intermediate tert-butyl N-(2-(benzoyl)benzyl)-N-methyl carbamate; (B) performing reduction on the intermediate tert-butyl N-(2-(benzoyl)benzyl)-N-methyl carbamate by a reductant, and performing acidolysis to obtain an intermediate 1-((2-(methylamino)methyl)phenyl)-1-phenylmethanol hydrochloride; and (C) performinga reaction on the intermediate 1-((2-(methylamino)methyl)phenyl)-1-phenylmethanol hydrochloride and chloroacetyl chloride to form an amide through a one-pot method, performing cyclization, and performing reduction by a reductant to obtain the objective compound nefopam hydrochloride. According to the invention, the reaction steps are simple, and the preparation method is easy to implement.
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- Old is Gold? Nefopam Hydrochloride, a Non-opioid and Non-steroidal Analgesic Drug and Its Practical One-Pot Synthesis in a Single Solvent for Large-Scale Production
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Nefopam hydrochloride is extensively used in most of the European countries until today as an analgesic because of its non-opiate (non-narcotic) and non-steroidal action with fewer side effects compared with opioid and other analgesics, which cause more troublesome side effects. A multikilogram synthesis of nefopam hydrochloride has been achieved in one pot using a single solvent (toluene). A ≥99.9% purity of the active pharmaceutical ingredient (API) was achieved in excellent overall yield (≥79%). The one-pot, five-step synthetic process involves formation of an acid chloride (3) from benzoylbenzoic acid (2) followed by amidation (4), reduction (5), cyclization (6), and formation of the hydrochloride salt (1). The major advantages include (i) use of a single solvent, (ii) >90% conversion in each step, (iii) a cost-effective and operationally friendly process, (iv) averting the formation of genotoxic impurities, and (v) improved overall yield (≥79%) provided by the one-pot operation. For the first time, we report the characterization data of API 1, intermediates 3, 4, and 5, and also a possible impurity (5a).
- Bodireddy, Mohan Reddy,Krishnaiah, Kiran,Babu, Prashanth Kumar,Bitra, Chaithanya,Gajula, Madhusudana Rao,Kumar, Pramod
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p. 1745 - 1751
(2017/11/24)
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- RACEMISATION OF ENANTIOMERS OF NEFOPAM AND ANALOGUES
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A process for the racemisation of a compound which is nefopam or an analogue thereof in the form of a single enantiomer or non-racemic mixture, which comprising contacting the compound with an acid.
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Page/Page column 4
(2008/06/13)
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