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

HRID 2282731Notes

Reaction equation

HRID 2282731 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-74b98fde2e9b4be995100e2de5db2c97
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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