288570-72-9

Upstream product

• 543-27-1 isobutyl chloroformate 
• 288570-67-2 2-methylpropyl (4-bromo-3-fluorophenyl)carbamate 
• 321430-28-8 3-fluorophenylcarbamic acid 2-methylpropyl ester 
• 372-19-0 meta-fluoroaniline 
• 1072-72-6 Tetrahydrothiopyran-4-one 
• 288570-70-7 2-methylpropyl [3-fluoro-4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate 

Downstream Products

• 288570-74-1 2-methylpropyl [4-(3,6-dihydro-1-oxido-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate 
• 288570-76-3 cis-2-methylpropyl [3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]carbamate 
• 188974-59-6 (S)-(-)-N-[[3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide 
• 288570-78-5 2-methylpropyl [3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate 

Relevant academic research and scientific papers

The synthesis of N-aryl-5(S)-aminomethyl-2-oxazolidinone antibacterials and derivatives in one step from aryl carbamates

Since 1993, a significant process research and development effort directed towards the large-scale synthesis of oxazolidinone antibacterial agents has been ongoing in both Early Chemical Process Research and Development, and Chemical Process Research and Development at Pharmacia. This work has led to the successful development of the current commercial process to produce Zyvox (linezolid), recently approved by the FDA as an antibacterial. While this synthesis is appropriate for the preparation of linezolid in particular, a more convergent and versatile synthesis was developed for the rapid preparation of numerous other oxazolidinone analogues. Toward this end, economical methods for the large-scale preparation of N-[(2S)-2-(acetyloxy)-3-chloropropyl]acetamide 3 and tert-butyl [(2S)-3-chloro-2-hydroxypropyl]carbamate 27 from commercially available (S)-epichlorohydrin via the common intermediate (2S)-1-amino-3-chloro-2-propanol hydrochloride 2a were developed. Also, general methods for coupling these reagents with N-aryl carbamates to give N-aryl-5(S)-aminomethyl-2-oxazolidinone derivatives in one step were developed. These reagents and procedures have proven widely applicable in the preparation of a diverse array of oxazolidinone analogues such as 23 and 28 in both process and medicinal chemistry research.

2-Fluoro-(oxid-thiopyran-4-yl)benzene derivatives

Compounds that can be used in the synthesis of cyclic sulfur-containing oxazolidinone antibacterial agents include2-Methylpropyl [4-(3,6-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate,4(R)-trans-[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl 3-nitrobenzenesulfonate,1α,4β(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanarnide monohydrate,4(R)-3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-(hydroxymethyl)-2-oxazolidinone,4(R)-[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl 3-nitrobenzenesulfonate.

Stereodivergent synthesis of sulfoxide-containing oxazolidinone antibiotics

Carbamate 5 was prepared under mild conditions via a novel metal-halogen exchange procedure without competing benzyne formation. Selection of an appropriate oxidation/reduction sequence afforded access to either the cis- or trans-1-oxo-4-aryltetrahydrothi