Reaktion #219997

Reaktionsgleichung

morpholin-4-yl-[5-(morpholin-2-ylmethoxy)-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-methanone

acetic acid

water

acetone

sodium cyanoborohydride

trifluoroacetate

→

desired product

Ausbeute 43.0%

[5-(4-Isopropyl-morpholin-2-ylmethoxy)-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-morpholin-4-yl-methanone

Ausbeute 43.0%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated in vacuo
2. 2
   workup.ADDITIONWater (5 mL) and hydrochloric acid (1N, 1.5 mL) were added to the residue
3. 3
   Waschenthe solution was washed with ethyl acetate
4. 4
   workup.ADDITIONbasified by addition of an aqueous solution of potassium carbonate
5. 5
   ExtraktionThe aqueous fraction was extracted with ethyl acetate
6. 6
   Waschenthe combined organic layers were washed with brine
7. 7
   SonstigeThe organic residue was purified on silica
8. 8
   Wascheneluting with 98:2 dichloromethane/methanol

Vorschrift

To a solution of morpholin-4-yl-[5-(morpholin-2-ylmethoxy)-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-methanone as trifluoroacetate salt (example 1, step 2, 120 mg, 1.0 eq.) in tetrahydrofuran (2 mL) were successively added water (0.004 mL, 1.1 eq.), acetone (0.019 mL, 1.5 eq.), acetic acid (0.040 mL, 3.0 eq.) and a solution of sodium cyanoborohydride in tetrahydrofuran (1M, 0.33 mL, 1.5 eq.). The reaction mixture was stirred at 55° C. overnight and concentrated in vacuo. Water (5 mL) and hydrochloric acid (1N, 1.5 mL) were added to the residue and the solution was washed with ethyl acetate and then basified by addition of an aqueous solution of potassium carbonate. The aqueous fraction was extracted with ethyl acetate and the combined organic layers were washed with brine. The organic residue was purified on silica, eluting with 98:2 dichloromethane/methanol, to yield 45 mg (43%) of the desired product as white foam. MS (m/e): 470.5 (MH+, 100%).

Quelle