(R)-[3-(3-Fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl]methyl methanesulfonate

Uses

(5R)-3-[3-Fluoro-4-(4-morpholinyl)phenyl]-5-[[(methylsulfonyl)oxy]methyl]-2-oxazolidinone (Linezolid USP Related Compound D) is an intermediate in the synthesis of Linezolid Dimer (L466520), an impurity of the antibacterial agent Linezolid (L466500).

Synthesis

To a 1L solution of dichloromethane containing 132.8 g of (R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-5-hydroxymethyl-2-oxazolidinone and 87.1 g of triethylamine was slowly added 74 g of methanesulfonyl chloride at 0°C under nitrogen protection. The reaction mixture was stirred at 0 °C for 30 min and then gradually warmed up to room temperature. A white solid precipitated during the reaction. Subsequently, a solvent mixture consisting of 1.75 L of water, 6.50 L of dichloromethane and 1 L of ethyl acetate was added to the reaction system and stirring was continued for 30 minutes. Upon completion of the reaction, the white solid product was collected by filtration. A final product of 140 g was obtained with a yield of 105.42% (w/w).

References

[1] Patent: WO2009/63505, 2009, A2. Location in patent: Page/Page column 14
[2] Patent: EP2163547, 2010, A1. Location in patent: Page/Page column 8
[3] Patent: WO2011/77310, 2011, A1. Location in patent: Page/Page column 12; 13
[4] Synthetic Communications, 2010, vol. 40, # 6, p. 789 - 798
[5] Patent: WO2010/84514, 2010, A2. Location in patent: Page/Page column 15