1,1'-Carbonyldiimidazole → 4-O-tert-butyl 1-O-[(Z)-(1,2-diamino-2-oxoethylidene)amino] (2R)-2-(3-cyclohexylpropyl)butanedioate

HRID 2183060Notes

Reaction equation

HRID 2183060 reaction equation
[C:1]([O:5][C:6](=[O:21])[CH2:7][C@@H:8]([CH2:12][CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:9]([OH:11])=[O:10])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.CN(C)N1C=CC=CC1.[NH2:43][C:44](=[N:48]O)[C:45]([NH2:47])=[O:46]>CN(C)C=O>[NH2:48]/[C:44](=[N:43]\[O:10][C:9]([C@H:8]([CH2:12][CH2:13][CH2:14][CH:15]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1)[CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:21])=[O:11])/[C:45]([NH2:47])=[O:46]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 6453552N,N-dimethylpyridin-1-amineHCID 9835906(2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acidHCID 534114201923816-07-2

Product 1

HCID 599097804-O-tert-butyl 1-O-[(Z)-(1,2-diamino-2-oxoethylidene)amino] (2R)-2-(3-cyclohexylpropyl)butanedioateYield 74.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-2-[2-(tert-Butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid (Preparation 1) (3.47 g, 11.6 mmol) in dimethylformamide (21 ml) was treated with 1,1′-carbonyldiimidazole (1.97 g, 12.2 mmol) and the mixture was stirred at ambient temperature for 1 hour. N-Dimethylaminopyridine (1.43 g, 11.7 mmol) was then added in one portion, followed by the addition of 2-amino-2-(hydroxyimino)acetamide (1.25 g, 12.1 mmol, Helv.Chim.Acta; 47; 1964; 33-46). The resulting mixture was stirred at room temperature for 24 hours. The mixture was partitioned between ethyl acetate and a 10% solution of citric acid in demineralised water. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with demineralised water (×4) and brine, dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduced pressure. The residue was crystallised from n-hexane, the precipitate was collected by filtration and dried in vacuo to afford the title compound as a colourless solid (3.30 g, 74% yield).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 24 hours
  2. customThe mixture was partitioned between ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. washThe combined organic layers were washed with demineralised water (×4) and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue was crystallised from n-hexane
  10. filtrationthe precipitate was collected by filtration
  11. customdried in vacuo

Sources & evidence

ORD record
ord-a283d8b2f6e64b36a91608fe16b4e662
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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