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0 °C

A suspension of (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-hydroxyacetate (7.20 g, 16.9 mmol) in neat t-BuOAc (100 mL) was cooled to 0° C. in an ice bath. 70% w/v aqueous HClO4 (293 μL, 3.4 mmol) was added dropwise over 5 min. The reaction was warmed to 23° C., then stirred for 2.3 h. At this point the reaction was transferred to an addition funnel. The reaction was added to a 23° C. solution of sat aqueous NaHCO3 (400 mL) over 30 min. Once addition was complete, the reaction was stirred for another 15 min. The resulting system was extracted with EtOAc (2×150 mL). Combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. Some residual t-BuOAc remained. Hexane (200 mL) was added and the slurry was concentrated once more. The resulting residue (reasonably free of t-BuOAc) was treated with Benzene and loaded onto a 330 g “gold” ISCO silica gel column. The following gradient elution sequence was used: [100% Hexane (5 column volumes, isocratic)→10% EtOAc/90% Hexane (5 column volumes, linear gradient→10% EtOAc/90% Hexane (5 column volumes, isocratic ((S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate elutes))→100% EtOAc (10 column volumes, isocratic, (unreacted (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-hydroxyacetate elutes))]. Product-containing fractions were pooled, concentrated, co-evarporated with Et2O (100 mL) to give desired product. LCMS-ESI+ calc'd for C22H23BrClNO3S: 496.0, 498.0 and 500.0 (M+H+); found: 496.2, 498.2, and 500.1 (M+H+). 1H NMR (400 MHz, CDCl3): δ 7.77 (s, 1H), 7.48 (m, 3H), 7.37 (m, 1H), 5.12 (s, 1H), 4.20 (m, 2H), 2.57 (s, 3H), 1.24 (t, 3H, J=7 Hz), 0.96 (s, 9H).

1. additionwas added dropwise over 5 min
2. temperatureThe reaction was warmed to 23° C.
3. customAt this point the reaction was transferred to an addition funnel
4. additionOnce addition
5. stirringthe reaction was stirred for another 15 min
6. extractionThe resulting system was extracted with EtOAc (2×150 mL)
7. dry with materialCombined organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. additionHexane (200 mL) was added
11. concentrationthe slurry was concentrated once more
12. additionThe resulting residue (reasonably free of t-BuOAc) was treated with Benzene
13. washThe following gradient elution sequence
14. concentrationconcentrated, co-evarporated with Et2O (100 mL)