Sodium hydride → Ethyl 5-((tert-butyldiphenylsilyloxy)methyl)-7-chloro-6-((2R,6S)-2,6-dimethylmorpholino)isoxazolo[4,5-b]pyridine-3-carboxylate

HRID 577912Notes

Reaction equation

HRID 577912 reaction equation
[H-].[Na+].[Si:3]([O:20][CH2:21][C:22]1[N:27]=[C:26]([C:28](=[N:34][OH:35])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:25](F)=[C:24]([Cl:37])[C:23]=1[N:38]1[CH2:43][C@H:42]([CH3:44])[O:41][C@H:40]([CH3:45])[CH2:39]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.[NH4+].[Cl-]>CN(C=O)C>[Si:3]([O:20][CH2:21][C:22]1[N:27]=[C:26]2[C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[N:34][O:35][C:25]2=[C:24]([Cl:37])[C:23]=1[N:38]1[CH2:43][C@H:42]([CH3:44])[O:41][C@H:40]([CH3:45])[CH2:39]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

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 136385143Ethyl 2-(6-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-((2R,6S)-2,6-dimethylmorpholino)-3-fluoropyridin-2-yl)-2-(hydroxyimino)acetate2×

Product 1

HCID 67356857Ethyl 5-((tert-butyldiphenylsilyloxy)methyl)-7-chloro-6-((2R,6S)-2,6-dimethylmorpholino)isoxazolo[4,5-b]pyridine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride, 60% dispersion in mineral oil (0.063 g, 1.56 mmol) was added to a flask and DMF, 5 ml, was added to give a white slurry. The mixture was cooled in an ice bath. Ethyl 2-(6-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-((2R,6S)-2,6-dimethylmorpholino)-3-fluoropyridin-2-yl)-2-(hydroxyimino)acetate (Intermediate 197, 0.786 g, 1.25 mmol) in 5 ml DMF was added to the sodium hydride suspension. There was some gas evolution, and the mixture became an orange solution. The reaction was worked up after 1 hour. Then saturated NH4Cl solution was added; the mixture was extracted with EtOAc, and washed with water (3×). The combined organic phase was dried over MgSO4 and concentrated. The residue was purified by chromatography on SiO2 using 0-40% EtOAc/hexanes to recover 544 mg (71%) of the title compound as a yellow foam.

Workup

  1. customto give a white slurry
  2. temperatureThe mixture was cooled in an ice bath
  3. extractionthe mixture was extracted with EtOAc
  4. washwashed with water (3×)
  5. dry with materialThe combined organic phase was dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on SiO2 using 0-40% EtOAc/hexanes
  8. customto recover 544 mg (71%) of the title compound as a yellow foam

Sources & evidence

ORD record
ord-05b4e1fd886c4b00aac82ff734169107
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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