Benzene → (+/-)-1-[[[3-(benzoylamino)-2-oxo-4-phenylbutyl]methylamino]carbonyl]-L-proline, phenylmethyl ester

HRID 1252160Notes

Reaction equation

HRID 1252160 reaction equation
Cl.[NH:2]1[CH2:16][CH2:15][CH2:14][C@H:3]1[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].CN1CC[O:21][CH2:20]C1.C(Cl)(Cl)=O.[CH:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.Cl.[CH3:35][NH:36][CH2:37][C:38](=[O:56])[CH:39]([NH:47][C:48](=[O:55])C1C=CC=CC=1)[CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(Cl)Cl>[C:48]([NH:47][CH:39]([CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:38](=[O:56])[CH2:37][N:36]([CH3:35])[C:20]([N:2]1[CH2:16][CH2:15][CH2:14][C@H:3]1[C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:5])=[O:21])(=[O:55])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 241BenzeneHCID 6371PhosgeneHCID 79724-Methylmorpholine2×HCID 2733413Proline benzyl ester hydrochlorideHCID 131713680(+/-)-N-[3-(Methylamino)-2-oxo-1-(phenylmethyl)propyl]benzamide, hydrochloride

Product 1

HCID 13753123(+/-)-1-[[[3-(benzoylamino)-2-oxo-4-phenylbutyl]methylamino]carbonyl]-L-proline, phenylmethyl esterYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

L-Proline, phenylmethyl ester, hydrochloride (300 mg., 1.25 mmole) is dissolved in 5 ml. of methylene chloride and N-methyl morpholine (0.35 ml., 3.13 mmole) is added. To this solution stirring at -20°, 12% phosgene solution in benzene (2 ml., approximately 1.9 mmole) is added. Stirring is continued at -20° for 30 minutes. The mixture is then evaporated, the residue is suspended in methylene chloride (5 ml.) and (±)-N-[3-(methylamino)-2-oxo-1-(phenylmethyl)propyl]benzamide, hydrochloride (250 mg., 0.76 mmole) is added followed by N-methyl morpholine (0.22 ml., 2 mmole). The reaction mixture is stirred overnight. It is then evaporated, the residue is dissolved in ethyl acetate and washed with saturated sodium bicarbonate, dilute hydrochloric acid, and water. The ethyl acetate solution after evaporation is chromatographed over silica gel using the solvent system, ethyl acetate:benzene (4:6) to give (±)-1-[[[3-(benzoylamino)-2-oxo-4-phenylbutyl]methylamino]carbonyl]-L-proline, phenylmethyl ester (37%) as an oil.

Workup

  1. stirringStirring
  2. customThe mixture is then evaporated
  3. stirringThe reaction mixture is stirred overnight
  4. customIt is then evaporated
  5. dissolutionthe residue is dissolved in ethyl acetate
  6. washwashed with saturated sodium bicarbonate, dilute hydrochloric acid, and water
  7. customThe ethyl acetate solution after evaporation
  8. customis chromatographed over silica gel using the solvent system, ethyl acetate:benzene (4:6)

Sources & evidence

ORD record
ord-d1cfcb8abac54e3596abcbdcfad20534
Source dataset
uspto-grants-1988_05
Patent number
US04742067

Reaction notes

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