Dimethylacetamide → HCID 86682583, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (±)-1-(5-bromo-2-ethoxycarbonylmethoxy-phenyl)-6,7-difluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (126 mg, 0.23 mmol, 1.00 eq.) in N,N-dimethylacetamide (0.45 mL) was added poly(methylhydrosiloxane) (5 μL) at r.t. The reaction mixture was heated to 120° C. and tris(dibenzylideneacetone) dipalladium(0) (4.5 mg, 0.005 mmol, 0.002 eq) then 1,1′-bis-(diphenylphosphino)-ferrocene (3.4 mg, 0.006 mmol, 0.027 eq.) were added. Afterwards, zinc cyanide (6.6 mg, 0.056 mmol, 0.25 eq.) was added. The resulting mixture was stirred at 150° C. during 25 min in a microwave. Zinc cyanide (3.3 mg, 0.028 mmol, 0.13 eq.), tris(dibenzylideneacetone) dipalladium(0) (2.3 mg, 0.002 mmol, 0.001 eq.) and 1,1′-bis-(diphenylphosphino)-ferrocene (1.7 mg, 0.003 mmol, 0.014 eq.) were added again. The resulting mixture was stirred at 150° C. during 25 min in a microwave. The reaction mixture was diluted with AcOEt and filtered over celite. The filtrate was washed with water, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by CC (SiO2, eluent:Hept/AcOEt) to yield the nitrile derivative as a pale yellow oil.

Provenance & Evidence