Hydroxylamine → (3s, 4r)-4-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid hydroxyamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid (0.280 g, 0.658 mmol) and 1-hydroxybenzotriazole (HOBT, 0.177 g, 1.32 mmol) in DMF (10 mL) was added 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (0.253 g, 1.32 mmol) at 0° C. The reaction mixture stirred at 0° C. for 10 min, then warmed to 25° C. over 1 h. After recooling the reaction to 0° C. hydroxylamine (50% by wt in water, 0.6 mL, 6.6 mmol) was added. The reaction was allowed to warm to 25° C. over 19 h. The DMF was removed in vacuo and the resulting oil was diluted with ethyl acetate (100 mL) and this mixture was then washed with saturated aqueous sodium bicarbonate (3×30 mL) and brine (30 mL). The organic layer was dried over MgSO4, filtered and concentrated to obtain a crude solid (0.170 g) which was purified by Biotage Flash 40S chromatography, eluting with 4% methanol in ethyl acetate, to afford (3S,4R)-4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid hydroxyamide as an amorphous white solid (0.02 g, 6.6%) that was a 75.7:24.3 mixture of enantiomers, as determined by analytical chiral HPLC (Chiralpak IA column, 7:3 n-propanol/heptane, 1 mL/min, 254 nm). MS: 472 (M+H)+

Provenance & Evidence