Sodium hydride → HCID 24992432, compound

HRID 1673214Notes

Reaction equation

HRID 1673214 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]([NH:8][CH:9]1[C:18]2[C:13](=[N:14][C:15]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[Cl:33])=[C:16]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)[CH:17]=2)[O:12][C:11]([CH3:35])([CH3:34])[CH2:10]1)=[O:7])=[O:4].[H-].[Na+]>CS(C)=O.CCOC(C)=O>[Cl:25][C:22]1[CH:21]=[CH:20][C:19]([C:16]2[CH:17]=[C:18]3[CH:9]([N:8]4[CH2:2][C:3](=[O:4])[NH:5][C:6]4=[O:7])[CH2:10][C:11]([CH3:34])([CH3:35])[O:12][C:13]3=[N:14][C:15]=2[C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=2[Cl:33])=[CH:24][CH:23]=1

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 67019941HCID 67019941, compound

Product 1

HCID 24992432HCID 24992432, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product obtained in Step A (127 mg, 0.23 mmol) was dissolved in DMSO (2 mL). NaH (20 mg, 0.51 mmol) was added and the reaction was stirred at rt for 1 h. The reaction was diluted with EtOAc and washed with a saturated NaHCO3 solution, 10% NaHSO4, brine, dried (Na2SO4), filtered and concentrated The residue was purified by flash chromatography on silica gel gradient eluted with 0-70% EtOAc in hexane to afford Example 113. Further purification on an AD column, eluting with 12% IPA/heptane provided the two pure enantiomers indicated below:

Workup

  1. washwashed with a saturated NaHCO3 solution, 10% NaHSO4, brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated The residue
  5. customwas purified by flash chromatography on silica gel gradient
  6. washeluted with 0-70% EtOAc in hexane
  7. customto afford Example 113
  8. customFurther purification on an AD column
  9. washeluting with 12% IPA/heptane
  10. customprovided the two pure enantiomers

Sources & evidence

ORD record
ord-8b90cdfa4e5140a68f792794af86ca75
Source dataset
uspto-grants-2011_08
Patent number
US07999107B2

Reaction notes

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