tert-butyl (2S)-2-amino-4-methylpentanoate → tert-Butyl (S)-2-((S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetate

HRID 1883097Notes

Reaction equation

HRID 1883097 reaction equation
[N-:1]=[C:2]=[O:3].[C:4]([O:8][C:9](=[O:16])[C@H:10]([CH2:12][CH:13]([CH3:15])[CH3:14])[NH2:11])([CH3:7])([CH3:6])[CH3:5].C(OC(=O)[C@H](CC(C)C)N)(C)(C)C.N[C@:31]([C:37]1[CH:42]=[CH:41][C:40]([Br:43])=[CH:39][CH:38]=1)([CH3:36])[C:32](OC)=[O:33]>CN(C=O)C>[Br:43][C:40]1[CH:39]=[CH:38][C:37]([C@@:31]2([CH3:36])[C:32](=[O:33])[N:11]([C@@H:10]([CH2:12][CH:13]([CH3:14])[CH3:15])[C:9]([O:8][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:16])[C:2](=[O:3])[NH:1]2)=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 7022311tert-butyl (2S)-2-amino-4-methylpentanoateHCID 69022991Methyl (S)-2-amino-2-(4-bromophenyl)propanoateHCID 86588629L-leucine tert-butyl ester isocyanate

Product 1

HCID 86588628tert-Butyl (S)-2-((S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetateYield 84.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4.8 g of L-leucine tert-butyl ester isocyanate (prepared from L-leucine tert-butyl ester analogously to J. S. Nowick et al., J. Org. Chem. 1996, 61, 3929) were added to a solution of 5.8 g (22.5 mmol) of 169.1 in 50 ml of DMF. After stirring at room temperature for 4 h, the solvent was removed and the residue was chromatographed on silica gel using heptane/tert-butyl methyl ether=6/4. The fractions containing the intermediate were combined, the solvent was removed in vacuo, the residue was dissolved again in 90 ml of absolute DMF and the solution was treated at 0° C. with 775 mg of a 55-65% strength sodium hydride dispersion in oil. After stirring at room temperature for 3 h, the solvent was removed in vacuo and the residue was chromatographed on silica gel using heptane/tert-butyl methyl ether=1/1. After concentration of the product fractions, 7.8 g (79%) of 169.2 were obtained as a colorless solid.

Workup

  1. customthe solvent was removed
  2. customthe residue was chromatographed on silica gel
  3. additionThe fractions containing the intermediate
  4. customthe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved again in 90 ml of absolute DMF
  6. additionthe solution was treated at 0° C. with 775 mg of a 55-65% strength sodium hydride dispersion in oil
  7. stirringAfter stirring at room temperature for 3 h
  8. customthe solvent was removed in vacuo
  9. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-a3e5fba4aaca4ac59a784ab2e0110cee
Source dataset
uspto-grants-2004_07
Patent number
US06759424B2

Reaction notes

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