Hydrochloric Acid → 5-(tert-Butyl-diphenyl-silanyloxy)-4,4-dimethyl-3-oxo-pentanenitrile

HRID 630970Notes

Reaction equation

HRID 630970 reaction equation
[H-].[Na+].C[O:4][C:5](=O)[C:6]([CH3:27])([CH3:26])[CH2:7][O:8][Si:9]([C:22]([CH3:25])([CH3:24])[CH3:23])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[C:29](#[N:31])[CH3:30].Cl>C1(C)C=CC=CC=1>[C:22]([Si:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[O:8][CH2:7][C:6]([CH3:27])([CH3:26])[C:5](=[O:4])[CH2:30][C:29]#[N:31])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 16067138Methyl 3-((tert-butyldiphenylsilyl)oxy)-2,2-dimethylpropanoate

Product 1

HCID 866872835-(tert-Butyl-diphenyl-silanyloxy)-4,4-dimethyl-3-oxo-pentanenitrileYield 25%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A suspension of sodium hydride (60% dispersion in oil) (2.12 g, 52.9 mmol) in toluene (65 mL) at reflux under N2 was added over 55 mins a solution of Intermediate 153a (15.93 g, assumed 37.8 mmol) and acetonitrile (2.87 mL, 54.9 mmol) in toluene (31 mL). The mixture was heated at reflux for 67 h. The cooled reaction mixture was slowly acidified to pH 5 with aqueous 1N HCl and extracted with EtOAc. The aqueous layer was extracted with EtOAc (×2) and the combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by FCC, using 0-50% ether in pentane, to give the title compound (3.52 g, 25%) as a yellow oil. LCMS (Method 3): Rt 4.94 min, m/z 402.3 [M+Na+].

Workup

  1. temperatureat reflux under N2
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 67 h
  4. customThe cooled reaction mixture
  5. extractionextracted with EtOAc
  6. extractionThe aqueous layer was extracted with EtOAc (×2)
  7. washthe combined organic phase was washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-27ca76ff0ec1486d8b10381e5cd7c518
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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