Triethylamine → HCID 178470715, compound

HRID 2293624Notes

Reaction equation

HRID 2293624 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([OH:22])=O)[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[NH:19])[NH:15][N+:16]([O-:18])=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[CH2:38]([O:40][C:41]([CH2:43][CH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)=[O:42])[CH3:39]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([N:47]1[CH2:48][CH2:49][CH:44]([CH2:43][C:41]([O:40][CH2:38][CH3:39])=[O:42])[CH2:45][CH2:46]1)=[O:22])[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[NH:19])[NH:15][N+:16]([O-:18])=[O:17])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 2760465Ethyl 2-(piperidin-4-yl)acetateHCID 178454200HCID 178454200, compound

Product 1

HCID 178470715HCID 178470715, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred and cooled suspersion of (S)-Nα -t-butoxycarbonyl-Nω -nitroarginine (3.1 g) in anhydrous tetrahydrofuran (THF) (50 ml) is added triethylamine (0.8 g) dropwise over 5 minutes at -20° C. and stirring is continued for a further 10 minutes. To the stirred mixture is then added isobutyl chloroformate (1.1 g) dropwise over 10 minutes at -20° C. and the mixture is stirred for a further 10 minutes. To the stirred mixture is then added 4-(ethoxycarbonylmethyl)piperidine (1.4 g) in THF (20 ml) dropwise over 10 minutes at -20° C. and then after stirring for a further 10 minutes at -20° the mixture is allowed to warm to room temperature with stirring for 1 hour. The reaction mixture is concentrated by evaporation and the residue is diluted with ethyl acetate (100 ml) and the mixture is washed with portions of water (3×15 ml), aqueous 5% NaHCO3 (2×15 ml), aqueous 10% citric acid (2×15 ml), then water (2×15 ml) and dried (MgSO4). Solvent is evaporated to give an oil which is chromatographed on silica gel using ethyl acetate as eluant to yield 1-((S)-Nα -t-butoxycarbonyl-Nω -nitroarginyl)-4-(ethoxycarbonylmethyl)piperidine as a pale yellow oil, Rf (ethanol)=0.16.

Workup

  1. stirringstirring
  2. stirringthe mixture is stirred for a further 10 minutes
  3. stirringafter stirring for a further 10 minutes at -20° the mixture
  4. stirringwith stirring for 1 hour
  5. concentrationThe reaction mixture is concentrated by evaporation
  6. additionthe residue is diluted with ethyl acetate (100 ml)
  7. washthe mixture is washed with portions of water (3×15 ml), aqueous 5% NaHCO3 (2×15 ml), aqueous 10% citric acid (2×15 ml)
  8. dry with materialwater (2×15 ml) and dried (MgSO4)
  9. customSolvent is evaporated
  10. customto give an oil which
  11. customis chromatographed on silica gel

Sources & evidence

ORD record
ord-8ae31363adae45d0a381e009c1617df1
Source dataset
uspto-grants-1997_11
Patent number
US05686564

Reaction notes

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