Triethylamine → HCID 69038583, compound

HRID 1351418Notes

Reaction equation

HRID 1351418 reaction equation
Cl.[N+:2]([O:5][CH2:6][CH2:7][CH2:8][O:9][C:10](=[O:21])[C@H:11]([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[NH2:12])([O-:4])=[O:3].[C:22]([O:26][C:27](=[O:48])[C@@H:28]1[CH2:32][CH2:31][CH2:30][N:29]1[C:33](=[O:47])[C@H:34](OS(C1C=CC(C)=CC=1)(=O)=O)[CH3:35])([CH3:25])([CH3:24])[CH3:23].C(N(CC)CC)C>CN(C=O)C.CCOCC>[C:22]([O:26][C:27](=[O:48])[C@@H:28]1[CH2:32][CH2:31][CH2:30][N:29]1[C:33](=[O:47])[C@H:34]([CH3:35])[NH:12][C@H:11]([C:10]([O:9][CH2:8][CH2:7][CH2:6][O:5][N+:2]([O-:4])=[O:3])=[O:21])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:24])([CH3:23])[CH3:25]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 69040749HCID 69040749, compoundHCID 86595721HCID 86595721, compound2×

Product 1

HCID 69038583HCID 69038583, compoundYield 46.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Homophenylalanine 3-nitrooxypropyl ester hydrochloride (3.85 g, 12.1 mmol) and N-[(2R)-2-(4-toluenesulfonyloxy) propionyl]-L-proline t-butyl ester (6.40 g, 16.1 mmol) were dissolved in DMF (15 mL) and triethylamine (3.9 mL, 28 mmol) was added to the solution. The reaction was stirred at room temperature for 48 hours, then N-[(2R)-2-(4-toluenesulfonyloxy)propionyl]-L-proline t-butyl ester (3.21 g, 8.1 mmol) was added again and the reaction stirred for further 48 hours. The reaction mixture was diluted with Et2O (100 mL), washed with brine (3×50 mL) dried over Na2SO4 and concentrated. The crude material was purified by flash chromatography (CHCl3/EtOAc 2:1) affording N-[(1S)-1-(3-nitrooxypropoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline t-butyl ester as a clear oil (2.84 g, 46%). The product was dissolved in CH3CN (20 mL), maleic acid was added (0.69 g, 5.9 mmol) and the solvent was removed. The crude material was crystallised from EtOAc/iPr2O affording N-[(1S)-1-(3-nitrooxypropoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline t-butyl ester hydrogen maleate as a white powder (2.27 g, 30%, 98%).

Workup

  1. stirringthe reaction stirred for further 48 hours
  2. washwashed with brine (3×50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography (CHCl3/EtOAc 2:1)

Sources & evidence

ORD record
ord-686c831e637548fe9c03a724abca8c26
Source dataset
uspto-grants-2007_05
Patent number
US07217733B2

Reaction notes

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