Sulfuric acid magnesium salt (1:1) → 3-nitrooxypropyl (2S)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]pyrrolidine-2-carboxylate

HRID 1351420Notes

Reaction equation

HRID 1351420 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]([NH:15][C@H:16]([C:18]([OH:20])=O)[CH3:17])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2].[N+:21]([O:24][CH2:25][CH2:26][CH2:27][O:28][C:29](=[O:35])[C@@H:30]1[CH2:34][CH2:33][CH2:32][NH:31]1)([O-:23])=[O:22].C([O-])(O)=O.[Na+].S([O-])([O-])(=O)=O.[Mg+2]>CCOC(C)=O.[Cl-].[Na+].O>[N+:21]([O:24][CH2:25][CH2:26][CH2:27][O:28][C:29](=[O:35])[C@@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[C:18](=[O:20])[C@H:16]([CH3:17])[NH:15][C@H:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)([O-:23])=[O:22]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 5702571N-[1(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanineHCID 11672975L-proline 3-nitrooxypropyl ester

Product 1

HCID 116773433-nitrooxypropyl (2S)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]pyrrolidine-2-carboxylateYield 40.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of 1,1-carbonylimidazole (22 g, 136 mmol) in EtOAc (150 mL) a solution of commercial N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine (20.2 g, 72.32 mmol) in EtOAc (100 mL) was added dropwise in 10 minutes. The resulting solution was stirred at room temperature for 1 hour then L-proline 3-nitrooxypropyl ester (28.8 g, 113 mmol) was added and the mixture was stirred for 16 hours. Then was treated with saturated NaHCO3 and brine. The organic layer was anhydrified with magnesium sulphate and concentrated. The residue was purified by flash chromatography (nHexane/EtOAc 4:6) affording N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline 3-nitrooxypropyl ester (14.2 g, 26%) as a pale yellow oil.

Workup

  1. additionwas added dropwise in 10 minutes
  2. stirringthe mixture was stirred for 16 hours
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography (nHexane/EtOAc 4:6)

Sources & evidence

ORD record
ord-abecd63970f94866a4fdd07e72aa2ee9
Source dataset
uspto-grants-2007_05
Patent number
US07217733B2

Reaction notes

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