Sodium hydride → HCID 86596863, compound

HRID 1171525Notes

Reaction equation

HRID 1171525 reaction equation
[Si:1]([O:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:16](=[O:33])[C@@H:17]([NH:22][C:23](=[O:32])[O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:18][CH2:19]SC)[C@H:11]([CH2:34][CH2:35][CH3:36])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+]>IC>[Si:1]([O:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH2:19][CH2:18][C@H:17]([NH:22][C:23](=[O:32])[O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:16]2=[O:33])[C@H:11]([CH2:34][CH2:35][CH3:36])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 86596862benzyl (S)-1-((1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-propylcyclohexylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate

Product 1

HCID 86596863HCID 86596863, compoundYield 24.7%

Reagents, catalysts & solvents 1

HCID 6328Methyl iodideSolvent

Conditions

Temperature
30 °C

Procedure

A sample of benzyl (S)-1-((1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-propylcyclohexylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate (4.0 g, 7.45 mmol) was dissolved in iodomethane (8 mL) and stirred at 30° C. for 3 days. The solution was concentrated in vacuo. The residue was dissolved in methylene chloride and the resultant solution was concentrated in vacuo again; this procedure was repeated twice before the residue was placed under high vacuum for 4 h. The resultant pale yellow foam solid was dissolved in THF (40 mL) and the resultant solution was cooled to 0° C. before being treated with sodium hydride (0.9 g, 37 mmol) in one portion. The mixture was slowly warmed to 30° C. and stirred for 12 h before being quenched with saturated ammonium chloride. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic phases were washed with brine, dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford benzyl (S)-1-((1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-propylcyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (0.9 g). MS found: (M+H)+=489.2.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. dissolutionThe residue was dissolved in methylene chloride
  3. concentrationthe resultant solution was concentrated in vacuo again
  4. waitwas placed under high vacuum for 4 h
  5. dissolutionThe resultant pale yellow foam solid was dissolved in THF (40 mL)
  6. temperaturethe resultant solution was cooled to 0° C.
  7. temperatureThe mixture was slowly warmed to 30° C.
  8. stirringstirred for 12 h
  9. custombefore being quenched with saturated ammonium chloride
  10. customThe organic layer was separated
  11. extractionthe aqueous layer was extracted with EtOAc
  12. washThe combined organic phases were washed with brine
  13. customdried
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a4e9accca96346d097c1c1817b44a73f
Source dataset
uspto-grants-2010_11
Patent number
US07829571B2

Reaction notes

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