Cyanoacetic acid → 3-[4-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)phenyl]-2-cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)propanamide

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Reaction Steps

2-Cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)acetamide (1 eq.), prepared from Amine 2 and cyanoacetic acid as detailed in Step 1 of Example 1, was dissolved in THF (0.1 M). At −78° C., potassium bis(trimethylsilyl)amide (15% w/w toluene solution, 1 eq.) was then added and the resulting yellow suspension was stirred at −78° C. for 15 min and at −40° C. for 15 min. tert-Butyl{3-[4-(iodomethyl)phenyl]propoxy}dimethylsilane from the previous step (1 eq.) was then added, at −78° C., as a 0.33 M THF solution over a period of 10 min. The resulting pale yellow mixture was allowed to warm slowly to RT over 5 h. The reaction was quenched with sat. aq. NH4Cl and extracted with ether. The combined organic extracts were washed with H2O and brine, dried over MgSO4 and filtered. Concentration of the filtrate in vacuo afforded a viscous yellow oil. Purification of the crude product thus obtained by way of column chromatography (SiO2, 10:1 (v/v) Hex:EtOAc→EtOAc) afforded the title compound as a colorless oil.

Provenance & Evidence