Methanol → HCID 68466290, compound

HRID 506160Notes

Reaction equation

HRID 506160 reaction equation
C([Li])CCC.[CH3:6][C:7]#[N:8].C[O:10][C:11](=O)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH2:21][Cl:22])[CH:14]=1.CO>C1COCC1.O.C(O)(=O)C>[Cl:22][CH2:21][CH2:20][O:19][C:15]1[CH:14]=[C:13]([CH2:12][C:11](=[O:10])[CH2:6][C:7]#[N:8])[CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 6342AcetonitrileHCID 22170578HCID 22170578, compoundHCID 178418339Butyllithium

Product 1

HCID 68466290HCID 68466290, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a 1.0 L three-necked round-bottomed flask was added 150 mL of anhydrous THF and cooled to −78° C. n-Butyl lithium (2.5 M in hexane, 52.5 mL, 131 mmol) was added dropwise. Anhydrous CH3CN (7.2 mL, 138 mmol) in 150 mL of anhydrous THF was subsequently added dropwise to the flask amidst stirring and cooling. After 1 h of stirring, [3-(2-chloroethoxy)phenyl]-acetic acid methyl ester (15 g, 66 mmol) in 20 mL of anhydrous THF was added dropwise to the resulting white colloidal mixture in the flask. The reaction mixture was stirred for an additional 2 h, followed by the addition of 4:1 mixture of MeOH: acetic acid (AcOH) at −78° C. The solution was diluted with 500 mL water and extracted with EtOAc (4×150 mL). The organic layer was separated, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. Residual AcOH was removed by concentrating in vacuo with toluene. The residue was passed through silica gel eluting with CH2Cl2 to yield 4-[3-(2-chloroethoxy)phenyl]-3-oxo-butyronitrile as an off-white solid, 16.0 g (99% yield).

Workup

  1. additionwas added dropwise
  2. temperaturecooling
  3. stirringAfter 1 h of stirring
  4. stirringThe reaction mixture was stirred for an additional 2 h
  5. customat −78° C
  6. extractionextracted with EtOAc (4×150 mL)
  7. customThe organic layer was separated
  8. dry with materialdried with anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customResidual AcOH was removed
  12. concentrationby concentrating in vacuo with toluene

Sources & evidence

ORD record
ord-7cc40f61b203406482f55f830deb816d
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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