Acetone, oxime → 1-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-3-fluoro-2-(propan-2-ylideneaminooxy)phenyl)ethanone

HRID 577823Notes

Reaction equation

HRID 577823 reaction equation
[CH3:1][C:2](=[N:4][OH:5])[CH3:3].C[C:7]([O-])([CH3:9])[CH3:8].[K+].[C:12]([SiH2:16][O:17][C:18](C1C=CC=CC=1)(C1C=CC=CC=1)[C:19]1[C:20]([N:30]2[CH2:35][C@H:34]([CH3:36])[O:33][C@H:32]([CH3:37])[CH2:31]2)=[C:21]([F:29])[C:22](F)=[C:23]([C:25](=[O:27])[CH3:26])[CH:24]=1)([CH3:15])([CH3:14])[CH3:13]>C1COCC1>[Si:16]([O:17][CH2:18][C:19]1[C:20]([N:30]2[CH2:31][C@H:32]([CH3:37])[O:33][C@H:34]([CH3:36])[CH2:35]2)=[C:21]([F:29])[C:22]([O:5][N:4]=[C:2]([CH3:3])[CH3:1])=[C:23]([C:25](=[O:27])[CH3:26])[CH:24]=1)([C:12]([CH3:15])([CH3:14])[CH3:13])([C:8]1[CH:7]=[CH:9][CH:14]=[CH:12][CH:13]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 67180Acetone, oximeHCID 23665647Potassium tert-butoxideHCID 178466840HCID 178466840, compound2×

Product 1

HCID 866580551-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-3-fluoro-2-(propan-2-ylideneaminooxy)phenyl)ethanoneYield 203%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of propan-2-one oxime (913 mg, 12.50 mmol) in THF (15 ml) was added KOtBu (935 mg, 8.33 mmol) at room temperature. After stirring for 45 minutes, 1-{5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorophenyl}ethanone (Intermediate 9, 2240 mg, 4.17 mmol) dissolved in 10 ml of THF was added. After stirring for 3 hours reaction quenched with saturated aqueous ammonium chloride solution and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, and concentrated to give the crude title compound (2.5 g). LCMS and NMR indicates >90% purity. Used in the next step without any further purification.

Workup

  1. additionwas added
  2. stirringAfter stirring for 3 hours
  3. customreaction
  4. customquenched with saturated aqueous ammonium chloride solution
  5. extractionextracted with EtOAc
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3da304cdb08e469b9677278ef2d2a6c8
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

Loading…