3,4-Dichlorobenzyl chloride → [(S)-1-(2-{[4-(3,4-Dichlorobenzyloxy)phenyl]-[(E)-(3-phenylacryloyl)]amino}-acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

Participants

Reaction Steps

3,4-Dichlorobenzyl chloride (15 μL) was added to a mixture of [(S)-1-(2-{(4-hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester 14 (50 mg, 0.11 mmol), cesium carbonate (52 mg, 0.16 mmol) and TBAI (40 mg, 0.11 mmol) in DMF (3 mL). The reaction mixture was stirred at room temperature overnight and then diluted with ethyl acetate and washed with 10% hydrochloric acid (×2) and brine, dried (Na2SO4) and evaporated to dryness. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate/petrol (2:1), to afford the title compound as a colourless foam (46 mg, 68%). 1HNMR (300 MHz) (CDCl3) δ1.41 (9H, s), 1.7-2.2 (2H, m), 3.35-3.8 (4H, m), 4.15-4.35 (2H, m), 4.5 (1H, m), 4.7-4.9 (1H, m), 5.01 (2H, s), 6.35 (1H, d, J=16 Hz), 6.93 (2H, d), 7.2-7.3 (6H, m), 7.37 (2H, d), 7.44 (1H, d), 7.52 (1H, br s) and 7.64 (1H, d, J=16 Hz).

Provenance & Evidence