Hydrochloric Acid → HCID 53374052, compound

Participants

Reaction Steps

To a 2-dram vial containing crude (R)-tert-butyl 5-(1-(4-(trifluoromethyl)phenylsulfonamido)ethyl)thiophene-2-carboxylate from Step 2 was added 1,2-dichloroethane (2 mL), and trifluoroacetic acid (0.246 mL, 3.20 mmol). After shaking at rt for 4 h, the mixture was evaporated to dryness to give a solid which was azeotroped with toluene (2×5 mL). To the resulting solid residue in another microwave vial was added HATU (0.0912 g, 0.240 mmol), N,N-dimethylformamide (1.5 mL), and triethylamine (0.178 mL, 1.28 mmol). The mixture was stirred for 10 min then O-(tert-butyldimethylsilyl)hydroxylamine (0.0471 g, 0.320 mmol) in DCM (0.5 mL) was added. The solution was shaken at rt for 2 h and then evaporated to dryness to afford a brown oil. To this oil in a microwave vial was added hydrochloric acid (3.5 mL, 1% in IPA). After shaking at rt for 30 min, solid NaHCO3 was added to quench the excess acid and the solvent was then removed. To the resulting solid residue was added DMSO (1.2 mL). After filtration, the DMSO solution was filtered and purified by Gilson prep-HPLC to give the title compound (0.0148 g, 23%) as a white solid. LC-MS: (FA) ES− 393. 1H NMR (Methanol-d4, 300 MHz) δ 7.92 (d, J=8.3 Hz, 2H), 7.76 (d, J=8.3 Hz, 2H), 7.24 (m, 1H), 6.77 (d, J=4.1 Hz, 1H), 4.78 (q, J=7.0 Hz, 1H), 1.44 (d, J=6.8 Hz, 3H).

Provenance & Evidence