The Synthetic Routes of Atorvastatin Cyclic Sodium Salt (Isopropyl) Impurity

Atorvastatin is a widely prescribed medication used to treat hyperlipidemia, a condition characterized by high levels of cholesterol and triglycerides in the blood.
The active ingredient in atorvastatin is atorvastatin calcium, which is a white or almost white, crystalline powder.
However, during the synthesis of atorvastatin, several impurities can be generated, including atorvastatin cyclic sodium salt (isopropyl).

Synthetic Routes of Atorvastatin Cyclic Sodium Salt (Isopropyl) Impurity

Atorvastatin is synthesized through a multi-step process that involves several chemical reactions.
One of the key steps in the synthesis of atorvastatin is the reaction between benzyl alcohol and a pinacol ester, which generates the intermediate compound (-)-1,1-dimethyl-2-[[2-(4-morpholinyl)-8-(2,2,2-trifluoro-1-hydroxy-3-(trifluoromethyl)propanamido)-9,10-dihydro-2H-pyrido[3,4-d]pyrimidin-7-yl]amino] phenyl}acetate.

This intermediate compound is then reduced to generate atorvastatin, which is the active ingredient in the medication.
However, during the synthesis of atorvastatin, impurities can be generated, including atorvastatin cyclic sodium salt (isopropyl).

The synthetic routes leading to the generation of atorvastatin cyclic sodium salt (isopropyl) impurity can vary depending on the specific synthesis process used.
However, several common synthetic routes are described below:

1. Reaction of (2S)-2-(difluoromethyl)-8-[2,2,2-trifluoro-1-(trimethylsilyl)-3-(trifluoromethyl)propanamido]-9,10-dihydro-2H-pyrido[3,4-d]pyrimidin-7-ylamino] phenyl acetate with potassium hydroxide

This route involves treating (2S)-2-(difluoromethyl)-8-[2,2,2-trifluoro-1-(trimethylsilyl)-3-(trifluoromethyl)propanamido]-9,10-dihydro-2H-pyrido[3,4-d]pyrimidin-7-ylamino] phenyl acetate with potassium hydroxide to generate atorvastatin cyclic sodium salt (isopropyl) impurity.

2. Reduction of (2S)-2-(difluoromethyl)-8-[2,2,2-trifluoro-1-(trimethylsilyl)-3-(trifluoromethyl)propanamido]-9,10-dihydro-2H-pyrido[3,4-d]pyrimidin-7-ylamino] phenyl acetate with lithium aluminum hydride

This route involves treating (2S)-2-(difluoromethyl)-8-[2,2,2-trifluoro-1-(trimethylsilyl)-3-(trifluoromethyl)propanamido]-9,10-dihydro-2H-pyrido[3,4-d]pyrimidin-7-ylamino] phenyl acetate with lithium aluminum hydride to generate atorvastatin cyclic sodium salt (isopropyl) impurity.

3. Reduction of (2S)-2-(difluoromethyl)-8-[2,2,2-