Dimethyl Sulfoxide → 2-(3-{[2,2-Difluoro-2-(4-fluoronaphthyl)ethyl]amino]-6-chloro-2-fluorophenyl)ethanal

Participants

Reaction Steps

To a solution of DMSO (470 mg, 6.0 mmol), DIEA (823 μL, 4.74 mmol) and 2-(3-{[2,2-difluoro-2-(4-fluoronaphthyl)ethyl]amino}-6-chloro-2-fluorophenyl)ethanol (723 mg, 1.82 mmol), as prepared in the preceding step, in DCM (55 mL) in an ice-bath was added sulfur trioxide pyridine complex (754 mg, 4.74 mmol). After stirring for 3.5 hours the reaction mixture was diluted with DCM (110 mL). The organic layer was separated, and the aqueous layer extracted with DCM (100 mL). The organic layers were combined, washed with 10% citric acid (3 times), H2O, and brine, dried over Na2SO4, and concentrated to give the title compound (722 mg, quantitative yield) as an orange oil. 1H-NMR (400 MHz, CDCl3) δ 9.69 (d, J=1.1 Hz, 1H), 8.22-8.18 (m, 2H), 7.67 -7.60 (m, 3H), 7.14 (t, J=9.2 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 6.49 (t, J=8.7 Hz, 1H), 4.20 (bs, 1H), 4.00 (dt, J=13.3, 6.7 Hz, 2H), 3.83 (s, 2H).

Provenance & Evidence