Toluene → Tert-butyl-5-(2-tetrahydropyran-2-yloxyethoxy)-2-azabicyclo[2.2.1]heptane-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Tert-butyl-5-hydroxy-2-azabicyclo[2.2.1]heptane-2-carboxylate (1.5 g, 7.0 mmol) and tetrabutylammonium bromide (0.35 g, 0.70 mmol) were stirred in sodium hydroxide (10 M) (30 mL, 1600 mmol)/toluene (30 mL) and heated to 60° C. 2-(2-Bromoethoxy)tetrahydropyran (4.4 g, 21 mmol) was added in 4 portions over 2 hours and heating continued overnight. Further 2-(2-bromoethoxy)tetrahydropyran (1 eq) was added and the reaction heated for a further 3 hours. The reaction mixture was diluted with DCM, washed with water, dried over Na2SO4 and concentrated in vacuo to afford a yellow oil. The reaction mixture was purified by flash chromatography, eluting with DCM then 90/10 DCM/MeOH to afford tert-butyl-5-(2-tetrahydropyran-2-yloxyethoxy)-2-azabicyclo[2.2.1]heptane-2-carboxylate (1.08 g).

Provenance & Evidence