Diisopropylcarbodiimide → HCID 131725968, compound

HRID 1242554Notes

Reaction equation

HRID 1242554 reaction equation
C(N=C=NC(C)C)(C)C.[C:10]([O:14][C:15]([N:17]1[CH2:21][C:20](=[N:22][O:23][CH3:24])[CH2:19][C@H:18]1[C:25]([OH:27])=O)=[O:16])([CH3:13])([CH3:12])[CH3:11].[C:28](=[N:31]O)([NH2:30])[CH3:29]>C(Cl)Cl.C1COCC1>[CH3:24][O:23][N:22]=[C:20]1[CH2:21][N:17]([C:15]([O:14][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:16])[C@H:18]([C:25]2[O:27][N:31]=[C:28]([CH3:29])[N:30]=2)[CH2:19]1

Participants

6

Reactant 3

HCID 12734Diisopropylcarbodiimide2×HCID 30926N-Hydroxyacetamidine2×HCID 58714586(2S,4EZ)-1(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid3×

Product 1

HCID 131725968HCID 131725968, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropylcarbodiimide (3.16 g, 25.17 mmol) was added to a solution of (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidine-carboxylic acid (Intermediate 2, 6.50 g, 25.17 mmol) and acetamidoxime (Intermediate 7, 1.86 g, 25.17 mmol) in DCM (55 ml) and stirred overnight at room temperature (DCM-insoluble amidoximes were pre-dissolved in THF, to which was added a solution of DIC and Intermediate 2 in DCM). After filtering at the pump, and evaporation in vacuo, the residue was dissolved in pyridine (60 ml) and refluxed for one hour, then cooled and allowed to stand overnight, then evaporated in vacuo. The crude product was then dissolved in DCM (50 ml) and washed with sat. NaHCO3(aq) (2×50 ml) and then 1M HCl(aq) (2×50 ml), dried over magnesium sulphate and evaporated in vacuo (crude yield 70%). Silica gel chromatography, eluting with 15% ethyl acetate in hexanes gave the desired compound, tert-butyl (2S,4EZ)-4-(methoxyimino)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-1-pyrrolidinecarboxylate (4.4 g, 60% yield).

Workup

  1. filtrationAfter filtering at the pump, and evaporation in vacuo
  2. dissolutionthe residue was dissolved in pyridine (60 ml)
  3. temperaturerefluxed for one hour
  4. temperaturecooled
  5. customevaporated in vacuo
  6. dissolutionThe crude product was then dissolved in DCM (50 ml)
  7. washwashed with sat. NaHCO3(aq) (2×50 ml)
  8. dry with material1M HCl(aq) (2×50 ml), dried over magnesium sulphate
  9. customevaporated in vacuo (crude yield 70%)
  10. washSilica gel chromatography, eluting with 15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-57b7603f52aa44faa2f4635bbf17bdea
Source dataset
uspto-grants-2006_10
Patent number
US07115639B2

Reaction notes

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