2,2,6,6-Tetramethylpiperidine → 4-(5-Tributylstannanyl-pyrazol-1-yl)-benzonitrile

Participants

Reaction Conditions

Reaction Steps

Hexyl lithium (2.3 M in hexanes) (16.96 mL, 39.01 mmol) was added to a stirred solution of 2,2,6,6-tetramethyl-piperidine (6.85 mL, 40.63 mmol) in dry THF (15 mL) at −30° C. and the resulting suspension was stirred for 20 minutes. The suspension was allowed to warm to 10° C. to aid dissolution and was added, via cannula, to a solution of 4-pyrazol-1-yl-benzonitrile (5.50 g, 32.51 mmol, prepared according to Bioorganic & Medicinal Chemistry Letters, 2006, 16(11), 2955-2959, which is incorporated herein by reference in its entirety) in THF (85 mL) at −78° C., keeping the internal reaction temperature<-50° C. The resulting reaction mixture was stirred at −75° C. for 4 hrs and tributyl tin(IV) chloride (9.08 mL, 33.49 mmol) was added keeping the internal reaction temperature<-60° C. during addition. The reaction mixture was stirred at −60° C. for 1.5 rsh then allowed to warm to RT. The resulting solution was quenched by addition of EtOAc (100 mL) and then washed with water (2×50 mL) followed by saturated brine (50 mL). The organic extract was dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was purified by flash chromatography, eluting with a gradient of 0-5% EtOAc in pentane to give the title compound as an amber oil that solidified on standing (10.11 g).

Provenance & Evidence