Sodium hydride → HCID 90199918, compound

HRID 930944Notes

Reaction equation

HRID 930944 reaction equation
[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[CH2:8]([S:10]([C:13]1[CH:14]=[CH:15][C:16](F)=[C:17]([C:19]2[C:20]3[CH:29]=[N:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:21]=3[C:22](=[O:26])[N:23]([CH3:25])[CH:24]=2)[CH:18]=1)(=[O:12])=[O:11])[CH3:9]>O1CCOCC1>[CH:1]1([CH2:4][O:5][C:16]2[CH:15]=[CH:14][C:13]([S:10]([CH2:8][CH3:9])(=[O:11])=[O:12])=[CH:18][C:17]=2[C:19]2[C:20]3[CH:29]=[N:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:36])([CH3:35])[CH3:37])[C:21]=3[C:22](=[O:26])[N:23]([CH3:25])[CH:24]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 75644Cyclopropanemethanol2×HCID 90200441HCID 90200441, compound

Product 1

HCID 90199918HCID 90199918, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Cyclopropylmethanol (0.018 g, 0.25 mmol) in dioxane (0.75 mL) was treated with sodium hydride (60% oil dispersion) (0.023 g, 0.587 mmol) and stirred at ambient temperature for 10 minutes. A solution of Example 322e (0.0683 g, 0.147 mmol) in dioxane (0.75 mL) was added and the mixture was stirred at 60° C. for 8 hours and then at ambient temperature for 16 hours. Additional cyclopropylmethanol (0.018 g, 0.249 mmol) and sodium hydride (60% oil dispersion) (0.023 g, 0.587 mmol) were added and the mixture was heated at 70° C. for 9 hours. The reaction mixture was cooled to ambient temperature and then partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 0 to 30% ethyl acetate in dichloromethane) to provide the title compound (0.0685 g, 90%).

Workup

  1. stirringthe mixture was stirred at 60° C. for 8 hours
  2. waitat ambient temperature for 16 hours
  3. temperaturethe mixture was heated at 70° C. for 9 hours
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (silica gel, 0 to 30% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-e71805944bf647b6bc23930305a00ec8
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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