Trifluoroacetic acid → HCID 57910774, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl 2-chloro-2-(hydroxyimino)acetate (3.15 g, 20.7 mmol) was added to a stirred solution of 1b (crude product from Step B; 6.91 mmol) and triethylamine (9.60 mL, 69.1 mmol) in THF (100 mL) at rt. After approximately 1 h, the reaction mixture was acidified to pH ˜1 by the addition of TFA, and the resulting mixture was heated to 50° C. After 1 h, the reaction mixture was concentrated in vacuo, the residue redissolved in TFA (30 mL) and the resulting solution was heated to 50° C. for an additional 1 h. After evaporation of the volatiles in vacuo, the crude residue was dissolved in EtOAc and carefully neutralized by the addition of saturated aqueous sodium bicarbonate. The organic layer was separated, dried (sodium sulfate), concentrated in vacuo, and the resulting crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-100% EtOAc/hexanes as eluent) to afford the title compound 1c. m/z (ES) 472 (MH)+. 1HNMR (500 MHz, CDCl3): δ 8.61 (d, 1H, J=3.5 Hz), 8.40 (d, 1H, J=2.2 Hz), 7.77 (m, 1H), 7.70 (d, 2H, J=8.5 Hz), 7.55 (d, 1H, J=7.7 Hz), 7.49 (d, 2H, J=8.4 Hz), 7.20 (m, 3H), 6.87 (s, 1H), 5.24 (s, 2H), 4.48 (q, 2H, J=7.1 Hz), 3.11 (m, 1H, J=6.6 Hz), 1.70 (s, 3H), 1.46 (t, 3H, J=7.1 Hz), 0.87 (d, 3H, J=6.7 Hz), 0.80 (d, 3H, J=6.9 Hz).

Provenance & Evidence