Reaction #41329

Reaction equation

2,2,2-trifluoro-N-((1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-yl)acetamide

2,2,2-Trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(3-methoxyphenyl)propan-2-yl]acetamide

aluminium chloride

→

product

Yield 42.2%

2,2,2-Trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(3-hydroxyphenyl)propan-2-yl]acetamide

Yield 42.2%

Solvents

methylbenzene

Conditions

Workup

1. 1
   OtherMethylbenzene was removed in vacuo
2. 2
   workup.ADDITIONthe solution in dodecanethiole was diluted with n-heptane (10 ml)
3. 3
   OtherOily precipitate has formed
4. 4
   Washwhich was washed with heptane
5. 5
   Otherdried in vacuo
6. 6
   workup.DISSOLUTIONdissolved in acetonitrile/water mixture
7. 7
   OtherThe crude product was purified by preparative HPLC

Procedure

To a stirred solution of 2,2,2-trifluoro-N-((1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-yl)acetamide (Example 6, 10 mg, 20 μmol) in methylbenzene (1 ml) was added dodecanethiole (1 ml), followed with anhydrous aluminium chloride (5.3 mg, 40 μmol). The mixture was stirred at 40° C. for 1 h. Methylbenzene was removed in vacuo, the solution in dodecanethiole was diluted with n-heptane (10 ml). Oily precipitate has formed, which was washed with heptane, dried in vacuo, and dissolved in acetonitrile/water mixture. The crude product was purified by preparative HPLC afforded 4 mg of product as a white solid (42%).

Source