The Production Process of Romifidine

Romifidine is a synthetic opioid analgesic drug that is used to treat moderate to severe pain.
The production process of Romifidine involves several steps, which are carried out in a meticulous manner to ensure the purity and efficacy of the final product.
In this article, we will discuss the production process of Romifidine in detail.

Step 1: Synthesis of N-[2-(dipropylamino)phenyl]-N-phenylacetamide
The first step in the production of Romifidine involves the synthesis of N-[2-(dipropylamino)phenyl]-N-phenylacetamide, which is also known as levophenacyl acetate.
This compound is synthesized by reacting phenylacetone with diethylpropionate in the presence of a suitable catalyst, such as aluminum chloride.
The reaction is then carried out under suitable conditions, such as in an inert solvent like dichloromethane, to yield N-[2-(dipropylamino)phenyl]-N-phenylacetamide.

Step 2: N-[2-(dipropylamino)phenyl]-N-phenylacetamide Hydrolysis
The next step in the production of Romifidine involves the hydrolysis of N-[2-(dipropylamino)phenyl]-N-phenylacetamide.
This is carried out by treating the compound with a suitable hydrolyzing agent, such as aqueous hydrochloric acid, under suitable conditions, such as in the presence of a solvent like methanol.
The hydrolysis reaction conversion the N-[2-(dipropylamino)phenyl]-N-phenylacetamide into N-[2-(dipropylamino)phenyl]-amide.

Step 3: N-[2-(dipropylamino)phenyl]-amide Halogenation
The next step in the production of Romifidine involves the halogenation of N-[2-(dipropylamino)phenyl]-amide.
This is carried out by treating the compound with a suitable halogenating agent, such as hydrogen chloride gas, under suitable conditions, such as in the presence of a solvent like acetic acid.
This reaction converts the N-[2-(dipropylamino)phenyl]-amide into N-[2-(dipropylamino)phenyl]-2-chloride amide.

Step 4: N-[2-(dipropylamino)phenyl]-2-chloride amide Reduction
The next step in the production of Romifidine involves the reduction of N-[2-(dipropylamino)phenyl]-2-chloride amide.
This is carried out by treating the compound with a suitable reducing agent, such as lithium aluminum hydride, under suitable conditions, such as in a solvent like tetrahydrofuran.
The reduction reaction converts the N-[2-(dipropylamino)phenyl]-2-chloride amide into N-[2-(dipropylamino)phenyl]-amide-2-ol.

Step 5: N-[2-(dipropylamino)phenyl]-amide-2-ol Demethylation
The next step in the production of Romifidine involves the demethylation of N-[2-(dipropylamino)phenyl]-amide-2-ol.
This is carried out by treating the compound with a suitable demethylating agent, such as hydrogen gas in the presence of a suitable catalyst, such as palladium on barium sulfate.
The reaction is then carried out under suitable conditions, such as in a solvent like ethanol, to yield N-[2-(dipropylamino)phenyl]-amide-2-ol.

Step 6: N-[2-(dipropylamino)phenyl]-amide-2-ol Halogenation
The final step in the production of Romifidine involves the halogenation of