Diisopropylamine → 1-tert-Butyl 4-ethyl 4-hydroxypiperidine-1,4-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

Under an inert atmosphere a 500 mL four necked round bottom flask (flame dried) with a mechanic stirrer was charged with 3.56 ml diisopropyl amine in 75 mL THF. At −10° C. 15.8 mL 1.6 N BuLi/hexane solution was added drop wise. The light yellow solution was stirred for 40 minutes at −10° C. and cooled then down to −75° C. 5.4 g ethyl 1-tert-butoxycarbonylpiperidine-4-carboxylate in 25 ml THF were added over 50 minutes and stirred for 3 h at −75° C. 5.5 g (2R,8S)-(+)-(camphorsulfonyl)oxaziridine in 80 mL THF were added drop wise over 1 h. The reaction was stirred for 2 h at −75° C. and then slowly warmed up over night to ambient temperature. The amber reaction solution was cooled to 5° C. and 150 mL saturated NH4Cl-solution, 50 mL water and 50 mL ethyl acetate was added and stirred for 10 minutes. The aqueous layer was separated and extracted once with 100 mL ethyl acetate. The organic layers were washed once with 200 mL brine, dried over Na2SO4, filtered off and concentrated under vacuum. The residue was purified over a silica cartridge eluting with a gradient formed from heptane and ethyl acetate to yield after evaporation of the product containing fractions 4.24 g (74%) of the title compound as light yellow viscous oil. MS (m/e): 174.2 [(M-Boc)+].

Provenance & Evidence