PREGABLIN ( LYRICA ) SYNTHESIS

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PREGABLIN








Pregabalin, also known as β-isobutyl-γ-Aminobutyric acid or Lyrica, is a medication used to treat epilepsy, neuropathic pain, anxiety disorders, and fibromyalgia.


The synthesis of pregabalin involves several steps starting from 4-methyl-2-pentanone. Here's a brief overview of the synthesis process:

1. Conversion of 4-methyl-2-pentanone to 4-methylvalerophenone: In this step, 4-methyl-2-pentanone is treated with ethylmagnesium bromide to yield 4-methylvalerophenone.
2. Formation of enamine: The 4-methylvalerophenone is reacted with cyclohexanone in the presence of base to form an enamine intermediate.
3. Alkylation: The enamine intermediate is alkylated with bromoacetic acid in the presence of base to form the key intermediate, 3-(2-bromoacetyl)-4-methylvalerophenone.
4. Cyclization: The key intermediate is cyclized with ammonia to form 3-(aminomethyl)-5-methyl-hexanoic acid, which is then converted to pregabalin by subsequent steps involving protection and deprotection of amino groups.

The complete synthesis reaction can be represented as follows:


Step 1: 4-methyl-2-pentanone + Ethylmagnesium bromide → 4-methylvalerophenone


Step 2: 4-methylvalerophenone + Cyclohexanone + Base → Enamine intermediate


Step 3: Enamine intermediate + Bromoacetic acid + Base → Key intermediate (3-(2-bromoacetyl)-4-methylvalerophenone)


Step 4: Key intermediate + Ammonia + Protection/deprotection steps → Pregabalin