Cesium carbonate → tert-butyl N-[4-[3-[4-(diethoxyphosphorylmethoxy)-2,6-dimethylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Participants

Reaction Steps

To a flask containing {[4-(4′-hydroxy-2′,6′-dimethyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 224: step b) 233 mg, 0.42 mmol), Cs2CO3 (137 mg, 0.42 mmol), DMF (2 mL), and trifluoro-methanesulfonic acid diethoxy-phosphorylmethyl ester (200 mg, 0.67 mmol, (Xu, Y. et al J. Org. Chem. 61, 7697 (1996); Phillion, D. et al Tetrahedron Lett. 27, 1477 (1986)) were added and heated to 50 C. This mixture was heated and stirred for 18 h under an Ar atmosphere. DMF was removed under vacuum and the residue was taken in EtOAc and washed with water and saturated NaCl. The EtOAc layer was separated dried over Na2SO4 and evaporated under vacuum to give an oil. This was purified by preparative thin-layer chromatography (EtOAc/Hexane) to give 94 (33%) of {3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-2,6-dimethyl-biphenyl-4-yloxymethyl}-phosphonic acid diethyl ester as a white solid. This solid was dissolved in dichloromethane (2 mL), and cooled in an ice bath. To this iodotrimethylsilane (Aldrich Chemical Company, 60 μL) was added and the mixture was stirred for 1 h at which time the dichloromethane was removed and the residue was taken in MeOH and treated with 6N HCl. This mixture was stirred for 3 h and the solvents were removed under high vacuum. To this residue a 50% solution of TFA in dichloromethane was added and the mixture was stirred for 1 h. TFA and dichloromethane were removed under vacuum and the residue was purified by preparative HPLC (Rev. Phase acetonitrile/water) which yielded the title compound as a white solid (30 mg, 33%). 1H-NMR (CD3OD): δ 7.8–7.7 (m, 2H), 7.62 (s, 1H), 7.5–7.3 (m, 2H), 6.7 (s, 2H), 3.77 (d, 2H, J=9.8 Hz), 2.44 (s, 3H), 1.74 (s, 6 H). ESI-MS (m/z): Calcd. for C21H23N2O6PS3: 527.1 (M+H); found: 527.1.

Provenance & Evidence