Reaktion #73383

Reaktionsgleichung

sodium hydroxide

2,4-dichloropyrimidine

5-hydroxy-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

5-hydroxy-N-(3-(trifluoromethyl)phenyl)indoline-1-carboxamide

sodium hydroxide

→

5-(2-chloropyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

Lösungsmittel

acetone

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGAfter additional 30 min stirring the reaction
2. 2
   Einengenis concentrated
3. 3
   workup.ADDITIONdiluted with EtOAc
4. 4
   Waschenwashed with water and brine before the organic layer
5. 5
   Trocknenis dried over sodium sulfate
6. 6
   Einengenconcentrated
7. 7
   SonstigeThe residue is separated via FCC (5-50% EtOAc in heptane)

Vorschrift

A mixture of 5-hydroxy-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide and 5-hydroxy-N-(3-(trifluoromethyl)phenyl)indoline-1-carboxamide (6:4) (3 g) is mixed with sodium hydroxide (0.45 g, 11.2 mmol) and 2,4-dichloropyrimidine (1.68 g, 11.2 mmol) in 50 mL of acetone and 50 mL of water at 0° C. and stirred for 1.5 h. Additional sodium hydroxide (0.075 g, 1.88 mmol) and (0.279 g, 1.88 mmol) are added. After additional 30 min stirring the reaction is concentrated, diluted with EtOAc, washed with water and brine before the organic layer is dried over sodium sulfate and concentrated. The residue is separated via FCC (5-50% EtOAc in heptane) to give 5-(2-chloropyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide. 1H NMR (400 MHz, CDCl3) δ ppm 8.45 (d, J=5.7 Hz, 1 H), 8.24 (d, J=9.0 Hz, 1 H), 7.86 (s, 1 H), 7.78 (d, J=8.2 Hz, 1 H), 7.60 (d, J=3.7 Hz, 1 H), 7.55 (t, J=8.0 Hz, 1 H), 7.45-7.50 (m, 2 H), 7.42 (d, J=2.1 Hz, 1 H), 7.15 (dd, J=8.9, 2.3 Hz, 1 H), 6.82 (d, J=5.7 Hz, 1 H), 6.73 (dd, J=3.7, 0.6 Hz, 1 H).

Quelle