Benzyl chloroformate → Benzyl (4-methylpiperidin-4-yl)carbamate

Participants

Reaction Steps

4-Amino-4-methyl-piperidine-1-carboxylic acid tert-butyl ester 80E (4.19 g, 19.6 mMol) was dissolved in a solution of 50 mL of dioxane and 20 mL of aqueous 2 N NaOH under an atmosphere of dry N2. To this solution was slowly added benzyl chloroformate (5.6 mL, 39 mMol) and the reaction was stirred for 3 hours at ambient temperature. The reaction mixture was concentrated under vacuum. The reaction mixture was dissolved in DCM and successively washed three with aqueous 1 N NaOH. The DCM layer was dried over Na2SO4, filtered and concentrated under vacuum to give a yellow oil. The oil was dissolved in 15 mL of TFA under an atmosphere of dry N2. The reaction mixture was concentrated under vacuum and partitioned between DCM and 0.1 N aqueous NaOH. The DCM layer was dried over Na2SO4, filtered and concentrated under vacuum to give 3.06 g of an oil. The oil was chromatographed on flash silica gel eluting with DCM to remove less polar impurities then with MeOH/DCM/NH4OH (20179.90.1) to give 2.85 g of the title compound 80F as an oil.

Provenance & Evidence