4-Methylmorpholine → N-[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline phenylmethyl ester

HRID 1906629Notes

Reaction equation

HRID 1906629 reaction equation
Cl.[CH2:2]([O:9][C:10](=[O:16])[C@@H:11]1[CH2:15][CH2:14][CH2:13][NH:12]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl.[CH2:18]([O:20][C:21]([C@@H:23]([NH:32][C@H:33]([C:35](O)=[O:36])[CH3:34])[CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:22])[CH3:19].CN1CCOCC1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C.C(Cl)Cl.C(Cl)Cl>[CH2:2]([O:9][C:10](=[O:16])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:35](=[O:36])[C@H:33]([CH3:34])[NH:32][C@H:23]([C:21]([O:20][CH2:18][CH3:19])=[O:22])[CH2:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733413Proline benzyl ester hydrochlorideHCID 18596335HCID 18596335, compound

Product 1

HCID 13105157N-[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline phenylmethyl esterYield 125.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To an ice-cooled solution of L-proline benzylester hydrochloride (0.58 g) and crude N-(1-(s)-Ethoxycarbonyl-3-Phenylpropyl)-L-Alanine Hydrochloride (0.73 g) in DMF/CH2Cl2 (1:1, 20 ml) is added N-methylmorpholine (0.53 g), followed by 1-hydroxybenzotriazole (0.38 g). After 15 min of stirring, a cold solution of dicyclohexylcarbodiimide (0.65 g) in dry methylenedichloride (6 ml) is added and the mixture stirred at 0°-5° C. for 1 hour, then allowed to cool at room temperature overnight. The mixture is filtered and the filtrate after washing with aqueous NaHCO3 concentrated in vacuo to dryness to give 1.35 g of yellow viscous oil [TLC (Silica gel; CHCl3 /acetone=9:1); Rf=0.4]. The crude product is used for next reaction without further purification.

Workup

  1. stirringthe mixture stirred at 0°-5° C. for 1 hour
  2. filtrationThe mixture is filtered
  3. washthe filtrate after washing with aqueous NaHCO3
  4. concentrationconcentrated in vacuo to dryness

Sources & evidence

ORD record
ord-a9b45dd905c84f25be98aeafa29a5786
Source dataset
uspto-grants-1987_03
Patent number
US04652668

Reaction notes

Loading…