Hydroxylamine → N'-hydroxy-3-(2-methylpropan-2-ylsulfinamido)-3,3-bis(3-(trifluoromethoxy)phenyl)propanamidine

Participants

Reaction Conditions

Reaction Steps

(R)—N-(2-Cyano-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)-2-methylpropane-2-sulfinamide (140 mg, 0.28 mmol) was stirred in EtOH (3 mL) and NH2OH in H2O (3 mL) in a capped microwave tube. The mixture was heated in an oil bath at 60-65° C. for 2 h. LC-MS (ESI) 528.42 (M+H), retention time=3.46 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run). The cap was removed and the solvents were concentrated. The residue was dissolved in CH2Cl2, washed with H2O, dried over MgSO4, filtered, and concentrated to give crude N′-hydroxy-3-(2-methylpropan-2-ylsulfinamido)-3,3-bis(3-(trifluoromethoxy)phenyl)propanamidine. After drying under vacuum for 2 h, the residue was dissolved in CH2Cl2 (5 mL). Et3N (0.25 mL, mmol, eq) was added followed by the addition of Ac2O (0.1 mL). The resulting mixture was stirred at room temperature for 24 h. LC-MS (ESI) 570.49 (M+H), 592.49 (M+Na), retention time=3.92 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run). CH2Cl2 (5 mL) was added. The organic layer was washed with H2O, dried over MgSO4, filtered, and concentrated to dryness to give colorless film (0.255 g). This residue was dissolved in HOAc (5 mL) and was heated at 90° C. for 4 h. After cooling, H2O was added. The mixture was extracted with CH2Cl2 (2×) and the combined organic portion washed with sat'd NaHCO3 (2×), H2O and brine, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, EtOAc/Hexanes=0 to 100%) to give 2-methyl-N-(2-(3-methylisoxazol-5-yl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)propane-2-sulfinamide as colorless oil (52 mg, total yield for 3 steps: 41%). LC-MS (ESI) 441.29 (M-NH2), retention time=3.14 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run); 1H NMR (400 MHz, CDCl3) δ ppm 7.26-7.19 (m, 5H), 7.00 (m, 3H), 3.57 (s, 2H), 2.39 (s, 3H).

Provenance & Evidence