4-Amino-1-Boc-piperidine → (S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylate

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Reaction Steps

To a stirred solution of tert-butyl 4-aminopiperidine-1-carboxylate (2.4 g, 12 mmol) in CH2Cl2 (30 mL) was added trimethylaluminum (6.0 mL, 12 mmol) dropwise. The resulting mixture was stirred for 15 minutes, then (S)-3-(4-bromo-2-fluoro-5-methylphenoxy)dihydrofuran-2(3H)-one (2.9 g, 10 mmol) in CH2Cl2 (30 mL) was added slowly and stirred at ambient temperature for 1 hour. The reaction was slowly quenched with 5% tartaric acid, neutralized with aqueous NaHCO3 and filtered through celite. The filtrate was extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylate (3.2 g, 6.5 mmol, 65% yield).

Provenance & Evidence