Reaction #3765

Reaction equation

N-hydroxysuccinimide

triethylamine

4-toluic acid

diphenyl chlorophosphate

→

4-toluic acid succinimidyl ester

Yield 94.0%

Solvents

ethyl acetate

methyl tert-butyl ether

ethyl acetate

Conditions

Workup

1. 1
   Temperaturethe reaction mixture warming to about 35° C
2. 2
   workup.STIRRINGThe mixture was stirred at room temperature for 1 hour until the reaction
3. 3
   Washthe organic phase was washed with 50 ml each of water, 2N hydrochloric acid and 10% strength aqueous sodium hydrogencarbonate solution
4. 4
   Otherevaporated
5. 5
   Other4.65 g of crude product were isolated
6. 6
   FiltrationThe white crystalline solid was filtered off
7. 7
   Otherdried at 50° C.

Procedure

2.42 g (0.021 mol) of N-hydroxysuccinimide and 5.06 g (0.050 mol) of triethylamine were initially introduced into 5 ml of ethyl acetate and the suspension was stirred at room temperature. 2.72 g (0.020 mol) of solid 4-toluic acid were added to this suspension in the course of 5 min. and then a solution of 5.64 g (0.21 mol) of diphenyl chlorophosphate was added dropwise in the course of 20 min., the reaction mixture warming to about 35° C. The mixture was stirred at room temperature for 1 hour until the reaction was complete. The reaction mixture was then diluted with 100 ml of ethyl acetate and the organic phase was washed with 50 ml each of water, 2N hydrochloric acid and 10% strength aqueous sodium hydrogencarbonate solution and then evaporated. 4.65 g of crude product were isolated, which was then stirred at room temperature for 30 minutes with 20 ml of methyl tert-butyl ether. The white crystalline solid was filtered off and dried at 50° C. and 10 mbar. 4.28 g (94%) of 4-toluic acid succinimidyl ester were isolated.

Source