1-Chloro-4-(chloromethyl)benzene → Ethyl-3-(4-chlorobenzyl)-N-Boc-piperidin-3-caroxylate

Participants

Reaction Steps

A solution of ethyl-N-boc-nipecotate (45 g, 0.18 mole) in tetrahydrofuran (200 mL) at -40° C. was treated with a solution of lithium bis (trimethylsilyl)amide in tetrahydrofuran (320 mL of a 1M solution). The solution was stirred at -40° for 15 minutes at which time 4-Chlorobenzyl chloride (34.59 g, 0.215 moles) was added and the reaction warmed to room temperature over 1.5 hours. The reaction was poured into saturated aqueous sodium bicarbonate (1 L) and extracted with ethyl acetate (3×500 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The residue was chromatographed on silica gel with 30% ethyl acetate/hexane as eluent to give 36.5 g.

Provenance & Evidence