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.

Key indicatorsSingle-crystal X-ray study T = 173 K Mean (C-C) = 0.002 Å R factor = 0.034 wR factor = 0.085 Data-to-parameter ratio = 18.0 For details of how these key indicators were automatically derived from the article, see

Key indicators: single-crystal X-ray study; T = 296 K; mean (C-C) = 0.007 Å; R factor = 0.058; wR factor = 0.148; data-to-parameter ratio = 10.2.The title compound, C 8 H 17 NO 2 ÁC 8 H 8 O 3 , exists as a complex with the base (pregabalin) in the predicted zwitterion form, based on the pK a differences between the acid and base. The asymmetric unit consists of two molecules of each component. The -NH 3 group adopts the standard propeller conformation. The structure forms pairs of hydrophobic and hydrophilic interactions along both the a and c axes. ExperimentalCrystal data C 8 H 17 NO 2 ÁC 8 H 8 O 3 M r = 311.37 Monoclinic, P2 1 a = 6.2922 (13) Å b = 27.423 (6) Å c = 10.009 (2) Å = 90.84 (3) V = 1726.9 (6) Å 3 Z = 4 Mo K radiation = 0.09 mm À1 T = 296 (2) K 0.22 Â 0.11 Â 0.05 mm Data collection Bruker APEXII CCD diffractometer Absorption correction: multi-scan (SADABS; Sheldrick, 2002) T min = 0.956, T max = 0.996 38738 measured reflections 4159 independent reflections 2488 reflections with I > 2(I) R int = 0.096