Methanol → HCID 68466290, compound

Participants

Reaction Steps

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).

Provenance & Evidence