N-Boc Protection of Amines with Di-tert-butyldicarbonate in Water under Neutral Conditions in the Presence of β-Cyclodextrin [1]

Abstract

A new protocol for protection of aryl and aliphatic amines was developed with (Boc)₂O in the presence of β-cyclodextrin in water. A catalytic amount of β-cyclodextrin is specific for ­activation of amines. This procedure works well on a wide variety of both electron-rich and electron-deficient amines.

β-cyclodextrin - amines - Boc-anhydride - Boc-derivatives - water

References and Notes

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General Procedure. β-Cyclodextrin (0.1 mmol of β-CD) was dissolved in H₂O (15 mL) at r.t. and the amine (1 mmol) dissolved in acetone-MeOH (1 mL) was added with stirring. Then (Boc)₂O
(1 mmol) was added and the reaction was stirred at r.t. for specific reaction times (Table [1] ). The reaction mixture was extracted with EtOAc and washed with brine. The organic phase was dried (Na₂SO₄), filtered and the solvent was removed under vacuum. The crude product was purified by silica gel column chromatography with EtOAc-hexane (1:9) as eluent. β-Cyclodextrin was recovered (95%) after lyophilization of the aqueous phase.