Water → HCID 59452684, compound

Participants

Reaction Steps

Oxalyl chloride (4.3 mL, 2.0M in DCM, 8.6 mmol) in 40 mL of DCM was cooled to −78° C. with stirring. DMSO (1.2 mL, 17 mmol) was added dropwise via addition funnel at such a rate so as to maintain the internal reaction temperature below −70° C. After ten min, 1-{4-nitro-3-[(2,2,2-trifluoroethyl)oxy]phenyl}-4-piperidinol (1.83 g, 5.71 mmol) in 8 mL of DMSO and 20 mL of DCM was added dropwise via addition funnel at such a rate so as to maintain the internal reaction temperature below −70° C. The addition funnel was rinsed with 10 mL of DCM, and the reaction was stirred for 1 h. TEA (4.0 mL, 29 mmol) was added dropwise via addition funnel, and the reaction was allowed to warm to rt. The reaction was poured into H2O, and the layers were separated. The aqueous layer was poured into saturated NaHCO3 (aqueous) and extracted with EtOAc. The DCM layer was washed with H2O and brine. The combined organic layers was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was triturated with 2:1 diethyl ether/EtOAc, filtered, and washed with diethyl ether. The yellow solid was collected to afford 1.63 g (90%) of the title compound of step C. 1H NMR (400 MHz, DMSO-d6) δ 7.94 (d, J=9.2 Hz, 1H), 6.70 (dd, J=9.5, 2.6 Hz, 1H), 6.63 (d, J=2.6 Hz, 1H), 4.94 (q, J=8.8 Hz, 2H), 3.82 (t, J=6.0 Hz, 4H), 3.02-3.13 (m, 2H), 1.16 (t, J=7.3 Hz, 2H).

Provenance & Evidence