Hydroxylamine → 1-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}4-[4-(trimethylsilylethynyl)phenyl]piperazine

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of 1-(methylsulfonyl)-4-[4-(trimethylsilylethynyl)phenyl]piperazine (673 mg, 2 mmol) in THF (13 mL) at −40° C., was added dropwise a solution of LiHMDS in THF (4.5 mL, 11.0M solution, 4.5 mmol). The resulting suspension was stirred at −40° C. for 10 minutes before being treated with chlorotrimethylsilane (254 μL, 2 mmol). The solution was then maintained at −40° C. for 10 minutes before being treated with a solution of (3S)-3-phenylbutanal (385 mg, 2.6 mmol, CAS number 53531-194) in THF (8 mL). The solution was allowed to warm to −15° C. over 1 hour before being quenched with a solution of hydroxylamine (1.23 mL, 50% aqueous solution in water, 20 mmol). The reaction was stirred for 3 hours at RT. The reaction was partitioned between ethyl acetate (30 mL) and water (30 mL). The combined organic extracts were then dried, (sat. brine and MgSO4), filtered and concentrated in vacuo. The residue was then purified by flash chromatography (silica, 30–40% ethyl acetate in iHexane) to give 1-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}-4-[4-(trimethylsilylethynyl)phenyl]piperazine (720 mg, 1.44 mmol, 68% @ 94 wt %).

Provenance & Evidence