N,N'-Dimethylethylenediamine → 10-[(R)-4-(2,2,2-trifluoro-1-hydroxy-ethyl)-phenyl]-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one

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Reaction Conditions

Reaction Steps

1,4-Dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one (352 mg, obtained in example 133, step 3) was dissolved in DMF (22 mL) at RT. Then, (R)-2,2,2-trifluoro-1-(4-iodophenyl)ethanol (755 mg, for synthesis see: J. Org. Chem. 2009, 74, 1605-1610), N,N′-dimethylethylenediamine (sym) (294 mg), cuprous iodide (476 mg) and K3PO4 (1.06 g) were added to the reaction mixture. The mixture was heated to 80° C. for 4.5 hours. The reaction mixture was cooled down to 30° C. and more 2,2,2-trifluoro-1-(4-iodophenyl)ethanol (252 mg) was added. The mixture was re-heated to 80° C. for 2 hours. The reaction mixture was cooled, poured into ice/water and extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane) to give the title compound as a colorless solid (415 mg, 62%). MS (ESI): 386.4 (MH+).

Provenance & Evidence