Reaction #1265420

Reaction equation

7-chloro-3-(piperidin-4-yl)-1H-indole

triethylamine

tert-butyl 3-bromopropionate

→

title resin

3-[4-(7-chloro-1H-indol-3-yl)piperidin-1-yl]propionic acid

Solvents

acetonitrile

Conditions

Workup

1. 1
   workup.ADDITIONA 25 mL round bottom flask was charged with polymer
2. 2
   TemperatureAfter cooling to room temperature
3. 3
   Filtrationthe resin was filtered off
4. 4
   Washwashed with dry acetonitrile (3×10 mL) and dry dichloromethane (3×10 mL)
5. 5
   workup.ADDITIONThe resin was treated for 20 minutes with 8 mL of a 1:1 mixture of dichloromethane and trifluoroacetic acid
6. 6
   workup.ADDITIONcontaining anisole (2%, w/w) and methionine (0.2%, w/w) (Caution: Generation of carbon dioxide)
7. 7
   FiltrationThe resin was filtered off
8. 8
   Washwashed with dry dichloromethane (10 mL)
9. 9
   workup.ADDITIONa 1:1 mixture of dichloromethane
10. 10
    OtherThe resin was dried in vacuo (20° C., 20 h)

Procedure

A 25 mL round bottom flask was charged with polymer bound 7-chloro-3-(piperidin-4-yl)-1H-indole (1.0 g, 0.98 mmol), triethylamine (80.2 mL), tert-butyl 3-bromopropionate and dry acetonitrile (5 mL). The mixture was stirred at 80° C. for 3 h. After cooling to room temperature, the resin was filtered off and washed with dry acetonitrile (3×10 mL) and dry dichloromethane (3×10 mL). The resin was treated for 20 minutes with 8 mL of a 1:1 mixture of dichloromethane and trifluoroacetic acid containing anisole (2%, w/w) and methionine (0.2%, w/w) (Caution: Generation of carbon dioxide). The resin was filtered off and washed with dry dichloromethane (10 mL), a 1:1 mixture of dichloromethane:triethylamine (3×10 mL) and dry dichloromethane (3×10 mL). The resin was dried in vacuo (20° C., 20 h) to yield the title resin (1.0 g).

Source