Potassium Carbonate → HCID 66884617, compound

A suspension of the crude regioisomeric mixture of 4-({tert-butoxycarbonyl-[1-(4-methoxy-benzyl)-1H-[1,2,3]triazol-4-ylmethyl]-amino}-methyl)-phenylboronic acid and 4-({tert-butoxycarbonyl-[3-(4-methoxy-benzyl)-3H-[1,2,3]triazol-4-ylmethyl]-amino}-methyl)-phenylboronic acid (1008 and 1009, 0.40 g, 0.89 mmol) and N-[3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide (1024, 0.37 g, 0.80 mmol, 0.90 equiv) in toluene (3 mL) was treated with powder K2CO3 (0.365 g, 5.31 mol, 3.0 equiv), EtOH (1 mL), and H2O (1 mL) at 25° C., and the resulting mixture was degassed three times under a steady stream of Argon at 25° C. Pd(PPh3)4 (51 mg, 0.09 mmol, 0.05 equiv) was subsequently added to the reaction mixture, and the resulting reaction mixture was degassed three times again under a stead stream of Argon at 25° C. before being warmed up to gentle reflux for 18 h. When TLC and HPLC/MS showed the coupling reaction was complete, the reaction mixture was cooled down to room temperature before being treated with H2O (20 mL) and ethyl acetate (20 mL). The two layers were then separated, and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with H2O (20 mL), 1.5 N aqueous HCl solution (2×20 mL), H2O (20 mL), and the saturated aqueous NaCl solution (20 mL), dried over MgSO4, and concentrated in vacuo. The residual oil was solidified upon standing at room temperature in vacuo to afford the crude {2′-Fluoro-4′-[2-oxo-5-(4-trimethylsilanyl-[1,2,3]triazol-1-ylmethyl)-oxazolidin-3-yl]-biphenyl-4-ylmethyl}-[1-(4-methoxy-benzyl)-1H-[1,2,3]triazol-4-ylmethyl]-carbamic acid tert-butyl ester (SC-167-63-1) as a regioisomeric mixture. This crude product (0.484 g, 0.592 g theoretical, 82%) was used directly in the subsequent reaction without further purification. For SC-167-63-1: 1H NMR (300 MHz, CDCl3) δ 0.299 and 0.31 (two s, 9H, Si(CH3)3), 1.44 and 1.48 (two br. s, 9H, N-BOC), 3.76 and 3.80 (two s, 3H, Ar—OCH3), 3.98-4.01 (dd, 1H, J=3.6, 1.8 Hz), 4.18-4.24 (t, 1H, J=9.0 Hz), 4.27-4.50 (m, 4H), 4.79-4.81 (m, 2H), 5.07-5.1 (br. s, 1H), 5.30 and 5.42 (two s, 2H), 6.81 and 6.89 (dd, 2H), 7.13-7.54 (m, 10H, aromatic-H), 7.74 (s, 1H, triazole-CH); C38H45FN8O5Si, LCMS (EI) m/e 741 (M++H) and 763 (M++Na).

1. additionA suspension of the crude
2. customthe resulting mixture was degassed three times under a steady stream of Argon at 25° C
3. customthe resulting reaction mixture
4. customwas degassed three times again under a stead stream of Argon at 25° C.
5. temperaturebefore being warmed up
6. temperatureto gentle reflux for 18 h
7. customthe coupling reaction
8. customThe two layers were then separated
9. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
10. washThe combined organic extracts were washed with H2O (20 mL), 1.5 N aqueous HCl solution (2×20 mL), H2O (20 mL)
11. dry with materialthe saturated aqueous NaCl solution (20 mL), dried over MgSO4
12. concentrationconcentrated in vacuo
13. customupon standing at room temperature in vacuo

ORD record

ord-05ac5eed11ef4028ad53d23d9c36f9e2

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399660B2