Acrylonitrile → 3-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)propanenitrile

Participants

Reaction Steps

A 100-mL RBF was charged with (9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methanol (2.318 g, 6.54 mmol), tetrabutylammonium hydrogen sulfate (0.111 g, 0.327 mmol), THF (32.7 mL), and acrylonitrile (2.154 mL, 32.7 mmol) to give a clear solution. NaOH (8.18 mL of a 2N aq. solution, 16.36 mmol) was added, and the resulting mixture was stirred for 1.5 h. The reaction mixture was diluted with EtOAc (70 mL), washed with water (2×50 mL), washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (0-10% MeOH/DCM) to give 3-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)propanenitrile as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=7.97 (d, J=2.4 Hz, 1 H), 7.45 (dd, J=2.5, 8.7 Hz, 1 H), 7.19 (dd, J=1.7, 2.9 Hz, 1 H), 7.09 (d, J=8.6 Hz, 1 H), 6.96-6.89 (m, 1 H), 3.77 (s, 3 H), 3.64 (t, J=6.0 Hz, 1 H), 3.54-3.42 (m, J=2.1 Hz, 3 H), 3.38-3.23 (m, 2 H), 2.85-2.74 (m, 2 H).

Provenance & Evidence