Acetonitrile → 5-Hydroxy-4,4-dimethyl-3-oxopentanenitrile

HRID 1809403Notes

Reaction equation

HRID 1809403 reaction equation
CO[C:3](=[O:16])[C:4]([CH3:15])([CH3:14])[CH2:5][O:6][Si](C(C)(C)C)(C)C.[C:17](#[N:19])[CH3:18].[H-].[Na+]>C1(C)C=CC=CC=1.Cl>[OH:6][CH2:5][C:4]([CH3:14])([CH3:15])[C:3](=[O:16])[CH2:18][C:17]#[N:19]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 12044793Methyl 3-(tert-butyldimethylsilyloxy)-2,2-dimethylpropanoate

Product 1

HCID 120447945-Hydroxy-4,4-dimethyl-3-oxopentanenitrileYield 90.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
110 °C

Procedure

A solution of 9.22 g of 3-(tert-Butyl-dimethyl-silanyloxy)-2,2-dimethyl-propionic acid methyl ester and acetonitrile (2.34 mL, 44.88 mmol) in toluene (25 mL) is added dropwise over 1 h at reflux to a suspension of 1.80 g (44.88 mmol) NaH (60% dispersion in mineral oil) in anhydrous toluene (50 mL). The reaction mixture is heated to 110° C. for 18 h. The reaction mixture is diluted with 1M aqueous HCl solution to pH 7 and extracted with ethyl acetate (3×200 mL). The organic layers are combined, washed with water and brine, dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to afford 4.79 g of 5-hydroxy-4,4-dimethyl-3-oxo-pentanenitrile as a dark biphasic oil which is used crude in the next step. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.17 (s, 6H), 3.55 (s, 2H), 3.61 (s, 2H). Spectrum recorded on crude material, signals of TBMDS are present.

Workup

  1. extractionextracted with ethyl acetate (3×200 mL)
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-20cd99508c0e4a93894786e1070054bb
Source dataset
uspto-grants-2013_01
Patent number
US08362039B2

Reaction notes

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