Acetonitrile → 3-(3,3-Dimethoxy-cyclobutyl)-3-oxo-propionitrile

HRID 1594397Notes

Reaction equation

HRID 1594397 reaction equation
[Li]CCCC.[C:6](#[N:8])[CH3:7].C[O:10][C:11]([CH:13]1[CH2:16][C:15]([O:19][CH3:20])([O:17][CH3:18])[CH2:14]1)=O.C(#N)C.C(=O)=O>C1COCC1>[CH3:18][O:17][C:15]1([O:19][CH3:20])[CH2:16][CH:13]([C:11](=[O:10])[CH2:7][C:6]#[N:8])[CH2:14]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10487446Methyl 3,3-dimethoxycyclobutane-1-carboxylateHCID 86587134Acetonitrile dry iceHCID 178418339Butyllithium

Product 1

HCID 575256253-(3,3-Dimethoxy-cyclobutyl)-3-oxo-propionitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 200 mL of THF at −78° C. was added n-BuLi (207.0 mL, 517.0 mmol, 2.5 M in hexanes). After the reaction temperature equilibrated (˜15 min), a solution of acetonitrile (27.0 mL, 517.0 mmol in 100 mL of THF) was added dropwise via addition funnel over a 20 min period. The resulting milky white slurry was allowed to stir one hr before a solution of 3,3-dimethoxy-cyclobutanecarboxylic acid methyl ester (45.0 g, 258.6 mmol in 150 mL of THF) was added down the side of the flask over a 20 min period. After one hr, the reaction was warmed to −45° C. (acetonitrile/CO2), and allowed to stir for two hr. The reaction was quenched cold by the dropwise addition of 2 N HCl (˜260 mL), pH=7 and then diluted with EtOAc (1 L). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×600 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to yield the title compound (quantitative yield) as a yellow oil that was used with out further purification. Rf 0.32 (40% EtOAc/hexanes). m/z (APCI+) 182 (M−1).

Workup

  1. custom(˜15 min)
  2. additionwas added down the side of the flask over a 20 min period
  3. customThe reaction was quenched cold by the dropwise addition of 2 N HCl (˜260 mL), pH=7
  4. additiondiluted with EtOAc (1 L)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with CH2Cl2 (2×600 mL)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-23e29d48da2d42da9bdd1edb4e13b13c
Source dataset
uspto-grants-2007_11
Patent number
US07300944B2

Reaction notes

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