Morpholine → 1-[[Methyl[(S)-3-[(4-morpholinylcarbonyl)amino]-2-oxo-4-phenylbutyl]amino]carbonyl]-L-proline, phenylmethyl ester

HRID 649516

Reaction equation

HRID 649516 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[N+](C1C=CC([O:14][C:15]([NH:17][C@@H:18]([CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:19](=[O:40])[CH2:20][N:21]([CH3:39])[C:22]([N:24]2[CH2:38][CH2:37][CH2:36][C@H:25]2[C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])=[O:23])=O)=CC=1)([O-])=O.N1CCC[C@H]1C(OCC1C=CC=CC=1)=O.C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH3:39][N:21]([CH2:20][C:19](=[O:40])[C@@H:18]([NH:17][C:15]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:14])[CH2:41][C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[C:22]([N:24]1[CH2:38][CH2:37][CH2:36][C@H:25]1[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:23]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8857Ethyl AcetateHCID 736155Benzyl L-prolinateHCID 141272261-[[[(S)-3-[[(4-nitrophenoxy)carbonyl]amino]-2-oxo-4-phenylbutyl]methylamino]carbonyl]-L-proline, phenylmethyl ester

Product 1

HCID 144994961-[[Methyl[(S)-3-[(4-morpholinylcarbonyl)amino]-2-oxo-4-phenylbutyl]amino]carbonyl]-L-proline, phenylmethyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Morpholine (1 ml., 11.4 mmole) is added to a stirring solution of 1-[[[(S)-3-[[(4-nitrophenoxy)carbonyl]amino]-2-oxo-4-phenylbutyl]methylamino]carbonyl]-L-proline, phenylmethyl ester (0.9 g., 1.58 mmole) in toluene at 0° in one portion. The reaction mixture turns yellow in 15 minutes and TLC indicates complete loss of starting material after 30 minutes. The resulting solution is washed sequentially with water, 1N hydrochloric acid, and 10% sodium bicarbonate. The organic layer is dried (MgSO4) and concentrated. The crude product is purified by preparative layer chromatography to give 0.26 g. of 1-[[methyl[(S)-3-[(4-morpholinylcarbonyl)amino]carbonyl]-2-oxo-4-phenylbutyl]amino]carbonyl]-L-proline, phenylmethyl ester as a yellow oil. TLC (ethyl acetate) Rf =0.18.

Workup

  1. waitTLC indicates complete loss of starting material after 30 minutes
  2. washThe resulting solution is washed sequentially with water, 1N hydrochloric acid, and 10% sodium bicarbonate
  3. dry with materialThe organic layer is dried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude product is purified by preparative layer chromatography
  6. customto give 0.26 g

Sources & evidence

ORD record
ord-4648a55d15244d76ace79333858c27d1
Source dataset
uspto-grants-1988_04
Patent number
US04740508

Linked notes

Loading…