Hydrochloric Acid → N-[(Phenylmethoxy)-carbonyl]-D-phenylalanyl-L-proline Methyl Ester

HRID 864094Notes

Reaction equation

HRID 864094 reaction equation
[C:1]([NH:11][C@@H:12]([C:20]([OH:22])=O)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH3:23][O:24][C:25](=[O:31])[C@@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]1.Cl.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.O>[CH3:23][O:24][C:25](=[O:31])[C@@H:26]1[CH2:30][CH2:29][CH2:28][N:27]1[C:20](=[O:22])[C@@H:12]([CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 79724-MethylmorpholineHCID 675678N-(Benzyloxycarbonyl)-D-phenylalanineHCID 853477Methyl L-prolinateHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 54358369N-[(Phenylmethoxy)-carbonyl]-D-phenylalanyl-L-proline Methyl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-CBZ-D-phenylalanine (47.3 g, 0.158 mmol) in DMF (300 mL) at 0° C., was added L-proline-methylester.HCl (25.0 g, 0.151 mmol), 1-hydroxybenzotriazole hydrate (20.28 g, 0.166 mmol), ethyl-3-(3-dimethylamino)-propyl carbodiimide.HCl (31.8 g, 0.166 mmol) and 4-methylmorpholine (16.0 g, 0.159 mmol). The reaction mixture was stirred for 8 h while allowing the reaction to warm to room temperature. The reaction mixture was poured in water (1.2 L) and extracted with ethyl acetate (3×300 mL). The combined organic extracts were washed as follows: KHSO4 (0.25M, 2×200 mL), water (1×200 mL), saturated aqueous NaHCO3 (2×200 mL) and saturated NaCl (1×200 mL). The organic layer was dried over MgSO4, filtered and the solvent removed in vacuo to give title compound, 60.9 g (98 %), as an oil.

Workup

  1. customthe reaction
  2. extractionextracted with ethyl acetate (3×300 mL)
  3. washThe combined organic extracts were washed
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-cf8c94d97a0241dca38ee4cfb9e7cb7b
Source dataset
uspto-grants-1996_10
Patent number
US05561146

Reaction notes

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