Sodium hydride → HCID 67358808, compound

HRID 577911Notes

Reaction equation

HRID 577911 reaction equation
[H-].[Na+].[Si:3]([O:20][CH2:21][C:22]1[C:23]([N:38]2[CH2:43][C@@H:42]([CH3:44])[O:41][C@H:40]([CH3:45])[CH2:39]2)=[C:24]([F:37])[C:25](F)=[C:26]([C:28](=[N:34][OH:35])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:27]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>CN(C=O)C>[Si:3]([O:20][CH2:21][C:22]1[C:23]([N:38]2[CH2:43][C@@H:42]([CH3:44])[O:41][C@H:40]([CH3:45])[CH2:39]2)=[C:24]([F:37])[C:25]2[O:35][N:34]=[C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:26]=2[CH:27]=1)([C:16]([CH3:17])([CH3:18])[CH3:19])([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 86658096HCID 86658096, compound2×

Product 1

HCID 67358808HCID 67358808, compoundYield 60.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (0.723 g, 18.07 mmol) was suspended in 60 ml of DMF and cooled in an ice bath. Ethyl 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6R)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-(hydroxyimino)acetate (Intermediate 166, 8.827 g, 14.45 mmol) was dissolved in 30 ml of DMF and added to the reaction flask. The ice bath was removed and the reaction stirred at room temperature for 2 hours. LCMS analysis indicated that the reaction was incomplete, so an additional 100 mg of NaH was added and the reaction stirred for 30 minutes. LCMS analysis indicated that the reaction was incomplete, so an additional 100 mg of NaH was added and the reaction stirred for 30 minutes. The reaction was cooled in an ice bath and quenched drop wise with 5 ml of saturated NH4Cl. The reaction was diluted with water and extracted three times with ethyl acetate. The organic layers were combined, washed 5× with brine, dried over MgSO4 and concentrated to give an oil. The oil was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate. Fractions were combined and concentrated to give the title compound (5.156 g, 8.73 mmol, 60.4%).

Workup

  1. temperaturecooled in an ice bath
  2. additionadded to the reaction flask
  3. customThe ice bath was removed
  4. additionso an additional 100 mg of NaH was added
  5. stirringthe reaction stirred for 30 minutes
  6. additionso an additional 100 mg of NaH was added
  7. stirringthe reaction stirred for 30 minutes
  8. temperatureThe reaction was cooled in an ice bath
  9. customquenched drop wise with 5 ml of saturated NH4Cl
  10. additionThe reaction was diluted with water
  11. extractionextracted three times with ethyl acetate
  12. washwashed 5× with brine
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated
  15. customto give an oil
  16. customThe oil was purified by silica gel column chromatography
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-d0ccfb2592ec4819a595384cc69ca0f0
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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