Fluticasone Impurity 18 synthesis

Yield:948566-11-8 89.48%

Reaction Conditions:

with water;dihydrogen peroxide;urea in N,N-dimethyl-formamide at 10 - 15; for 0.5 h;

Steps:

22

Example 22 ^α-Difluoro-lVc-KZ-furanylcarbony^oxyl-lly-hydroxy-lα-methyl-3-oxoandrosta-l^- diene-17 β-carbonylsulfenic acidA solution of urea-hydrogen peroxide (2.41g, 0.0256mol) in jV,N-dimethylformamide was added at 10 to 15°C into a clear solution of 6α,9α-difluoro-17α-[(2-furanylcarbonyl)oxy]-l β- hydroxy-16α-methyl-3-oxoandrosta-l,4-diene-17 β-carbothioic acid (13.Og, 0.0256mol) in N, N- dimethylformamide (40ml). The reaction mixture was stirred at 10-15⁰C for 30min, then poured into ice-water. The solid was filtered, washed with water, and dried at 50-60⁰C to yield the title compound as white solid (12.0g, 89.48%). ¹H NMR (400 MHz in CDCI3+DMSO-d6), δ : 1.06(d, J=7.09Hz, 3H), 1.19(s, 3H), 1.33- 1.38(m, IH), 1.55(s, 3H), 1.58-l.98(m, 4H), 2.26-2.52(m, 4H), 3.02-3.06(m, IH), 4.32-(br-d, J=8.76Hz, IH), 5.14-5.19(br-s, IH), 5.38-5.54(m, IH), 6.29(s, IH), 6.30(d, ./=8.7 IHz, IH), 6.54(dd, J|=3.32Hz, J2=l-53Hz, IH), 7.08(d, J=3.37Hz, IH), 7.27(d, 7-10.30Hz, IH), 7.67(s, IH).

References:

WO2007/99548,2007,A2 Location in patent:Page/Page column 49-50