Reaction #216020

Reaction equation

1-hydroxybenzo-triazole

N-trifluoroacetamide

D-tryptophan

benzylamine

1,3-dicyclohexylcarbodiimide

→

(R)-N-(phenylmethyl)-α-[(trifluoroacetyl)amino]-1H-indole-3-propanamide

Yield 66.0%

Solvents

THF

Conditions

Workup

1. 1
   TemperatureThe solution was maintained at 0°-5° C. for 1 hour
2. 2
   FiltrationThe mixture was filtered
3. 3
   Washthe collected solids were washed with ethyl acetate
4. 4
   ConcentrationThe filtrate was concentrated to an oil that
5. 5
   workup.DISSOLUTIONwas dissolved in 250 mL of ethyl acetate
6. 6
   WashThe solution was washed sequentially with 250 mL portions of 10% aqueous acetic acid, water, 5% aqueous sodium hydrogen carbonate, water and brine
7. 7
   Dryingdried (NaSO4 )
8. 8
   Concentrationconcentrated to a solid
9. 9
   OtherCrystallization from 170 mL of 65:35 2-propanol

Procedure

An ice-cold solution of 15 g (50 mmol) of the N-trifluoroacetamide of D-tryptophan, synthesized by methods previously outlined (J. Org. Chem. 1979;44:2805-2807) in 50 mL of THF under N2 was treated sequentially with 7.1 g (52.5 mmol) of 1-hydroxybenzo-triazole then 10.83 g (52.5 mmol) of 1,3-dicyclohexylcarbodiimide. After 15 minutes, the solution was treated with 5.74 mL (52.6 mmol) of benzylamine. The solution was maintained at 0°-5° C. for 1 hour, then let warm to 25° C. overnight. The mixture was filtered and the collected solids were washed with ethyl acetate. The filtrate was concentrated to an oil that was dissolved in 250 mL of ethyl acetate. The solution was washed sequentially with 250 mL portions of 10% aqueous acetic acid, water, 5% aqueous sodium hydrogen carbonate, water and brine, then dried (NaSO4 ), and concentrated to a solid. Crystallization from 170 mL of 65:35 2-propanol:petroleum ether afforded 12.81 g (66% ) of (R)-N-(phenylmethyl)-α-[(trifluoroacetyl)amino]-1H-indole-3-propanamide [II: R1 =H, R2 =CH2CH(NHCOCF3)CONHCH2Ph, R3 =H] as an off-white solid which was used directly in the next reaction; mp 186°-188° C.

Source