Trifluoroacetic acid → HCID 19426806, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of the product of Step 1, above (10, 0.5 g, 1.5 mmol), in triethylamine (4 ml) was added bis(triphenylphosphine)palladium (II) chloride (55 mg, 0.078 mmol) and N,O-bis(tert-butoxycarbonyl)-N-(3-butyn-2-yl)hydroxylamine (840 mg, 2.8 mmol) in triethylamine (1 ml) under a N2 atmosphere. The reaction mixture was stirred at 75° C. for 1.5 hours, then concentrated under reduced pressure. The residue was extracted with ethyl acetate (3×10 ml) and the organic layer was washed with 1N HCl (10 ml), saturated aqueous NaHCO3 (10 ml) and brine (10 ml). The combined extracts were dried over MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel (ethyl acetate:n-hexane=1:6) to give N,O-bis(tert-butoxycarbonyl)-[4-(3-[4,5-dihydro-3-(4-fluorophenyl)isoxazol-5-yl]phenyl)-3-butyn-2-yl]hydroxylamine. To a solution of the protected hydroxylamine thus obtained, in CH2Cl2 (3 ml) cooled to 0° C., was slowly added TFA (0.72 ml, 9.3 mmol). The reaction mixture was allowed to warm to room temperature over 2 hours. The reaction mixture was poured into ice cold saturated aqueous NaHCO3 (20 ml) and extracted with CH2Cl2 (3×15 ml). The combined extracts were washed with water (30 ml) and brine (30 ml) and were dried over MgSO4. After evaporation of solvent, the residue was chromatographed on silica gel (ethyl acetate:n-hexane=1:1) to give the title compound (11, 178 mg, 69% yield) as orange solids.

Provenance & Evidence