Reaction #77823

Reaction equation

(S)-1-(4-chlorophenyl)ethylamine

N-chloro-carbamoyl-4-[(4-cyclohexylphenylamino)methyl]benzoic acid methyl ester

triethylamine

NMP

→

4-[3-[1(S)-(4-Chlorophenyl)ethyl]1-(4-cyclohexylphenyl)ureidomethyl]benzoic acid methyl ester

Conditions

Workup

1. 1
   OtherA 2 l reaction flask
2. 2
   Otherequipped
3. 3
   Otherthe internal reaction temperature below 30° C
4. 4
   workup.STIRRINGStirring
5. 5
   Otherthe reaction mixture was partitioned between water (1.0 l) and ethyl acetate (1.0 l)
6. 6
   OtherAfter extensive mixing, the organic layer was separated
7. 7
   Washwashed with a 5% aqueous solution of citric acid (500 ml), and saturated ammonium chloride (500 ml)
8. 8
   Dryingbefore drying with anhydrous sodium sulfate
9. 9
   OtherSolvent was removed
10. 10
    Otherthe residual oil was evaporated once from acetonitrile
11. 11
    OtherThis product was sufficiently pure for further synthesis

Procedure

A 2 l reaction flask equipped with mechanical stirring was charged with N-chloro-carbamoyl-4-[(4-cyclohexylphenylamino)methyl]benzoic acid methyl ester (94 g, 0.244 mol), NMP (1.0 l) and triethylamine (68 ml, 0.487 mol). To the clear solution was added drop wise (S)-1-(4-chlorophenyl)ethylamine (38.0 g, 0.244 mol), keeping the internal reaction temperature below 30° C. Stirring was continued for 2 hours, then the reaction mixture was partitioned between water (1.0 l) and ethyl acetate (1.0 l). After extensive mixing, the organic layer was separated, and washed with a 5% aqueous solution of citric acid (500 ml), and saturated ammonium chloride (500 ml), before drying with anhydrous sodium sulfate. Solvent was removed, and the residual oil was evaporated once from acetonitrile. This product was sufficiently pure for further synthesis. Yield: 103 g (84%).

Source