Trifluoroacetic acid → HCID 86679005, compound

Participants

Reaction Steps

A solution of the intermediate from Step B above (102 mg, 0.182 mmol) stirred in THF (3566 μl) was added 2-tert-butyl-1,1,3,3-tetramethylguanidine (34.2 μl, 0.182 mmol) followed by 2-bromoacetonitrile (19.02 μl, 0.273 mmol). After stirring for 5 minutes at room temperature, saturated aqueous NH4Cl was added. The reaction mixture reaction was then partitioned between EtOAc and water. The organic layer was dried (sodium sulfate), filtered and concentrated in vacuo. The crude material was taken up in DCM (1 mL) and TFA (280 μl, 3.64 mmol) was added. After 3 hours the reaction was quenched with aq. NaHCO3 and partitioned between water and EtOAc. The organic layer was dried, concentrated in vacuo and purified by silica gel column chromatography using a hexanes/EtOAc gradient to afford the product as a white solid. Chiral separation using SFC provided both enantiomers of the title compound. 1H NMR (500 MHz, CHCl3-d): δ 8.45 (d, J=8.72 Hz, 1H); 7.43 (s, 1H); 7.18 (dd, J=8.75, 1.62 Hz, 1H); 5.48 (s, 2H); 4.71 (t, J=7.69 Hz, 2H); 2.99 (d, J=16.98 Hz, 1H); 2.81-2.68 (m, 2H); 2.67 (d, J=16.98 Hz, 1H); 1.68 (s, 3H). m/z=500.0 (M+H).

Provenance & Evidence