N,N,N',N'-Tetramethylethylenediamine → 3-Ethyl-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]benzonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of Intermediate 1 (2.9 g, 9.7 mmol), sodium cyanide (950 mg, 19.4 mmol), palladium (II) acetate (109 mg, 0.49 mmol), TMEDA (2.2 mL, 14.9 mmol), and 1,5-dis(diphenylphosphino)pentane (855 mg, 1.94 mmol) in mesitylene (50 mL) was bubbled with argon for 10 min. The degassed reaction mixture was heated to 170° C. for 16 h. After cooling to RT, the reaction mixture was diluted with water, stirred for another 10 min then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated. Purification by MPLC (40% ethyl acetate in hexanes) gave rise to 2.23 g of Intermediate 4 as colorless oil.

Provenance & Evidence