Reaction #1265419

Reaction equation

7-chloro-3-(1-tert-butoxycarbonylpiperidin-4-yl)-1H-indole

diisopropylethylamine

→

title resin

Yield 199.9%

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

Yield 199.9%

Solvents

dimethyl formamide

Conditions

Workup

1. 1
   TemperatureAfter cooling to room temperature
2. 2
   Filtrationthe resin was filtered off
3. 3
   Washwashed with dry dimethyl formamide (3×25 mL), dry acetonitrile (3×25 mL) and dry dichloromethane (3×25 mL)
4. 4
   workup.ADDITIONThe resin was then treated for 20 minutes with 60 mL of a 1:1 mixture of dichloromethane and trifluoroacetic acid
5. 5
   workup.ADDITIONcontaining anisole (2%, w/w) and methionine (0.2%, w/w)
6. 6
   workup.STIRRINGto agitate the resin (Caution: Generation of carbon dioxide)
7. 7
   FiltrationThe resin was filtered off
8. 8
   Washwashed with dry dichloromethane (25 mL)
9. 9
   workup.ADDITIONa 1:1 mixture of dichloromethane
10. 10
    OtherThe resin was dried in vacuo (20° C., 20 h)

Procedure

A 100 mL round bottom flask was charged with 4-nitrophenyloxycarbonyloxyethyl polystyrene (4.0 g, 4.3 mmol), 7-chloro-3-(1-tert-butoxycarbonylpiperidin-4-yl)-1H-indole (2.7 g, 8.1 mmol), diisopropylethylamine (3.5 mL, 20.2 mmol), 4-dimethylaminopyridine (0.5 g, 4 mmol) and dry dimethyl formamide (50 mL). The mixture was stirred at 90° C. for 72 h. After cooling to room temperature, the resin was filtered off and washed with dry dimethyl formamide (3×25 mL), dry acetonitrile (3×25 mL) and dry dichloromethane (3×25 mL). The resin was transferred to a 250 mL glass cylinder with a fritte and a three way junction in the bottom. The resin was then treated for 20 minutes with 60 mL of a 1:1 mixture of dichloromethane and trifluoroacetic acid containing anisole (2%, w/w) and methionine (0.2%, w/w), using a flow of nitrogen to agitate the resin (Caution: Generation of carbon dioxide). The resin was filtered off and washed with dry dichloromethane (25 mL), a 1:1 mixture of dichloromethane:triethylamine (3×25 mL) and dry dichloromethane (3×25 mL). The resin was dried in vacuo (20° C., 20 h) to yield the title resin (3.8 g).

Source