1,3-Cycloheptadiene → Tert-butyl 6-oxa-7-azabicyclo[3.2.2]non-8-ene-7-carboxylate

Temperature

0 °C

(1Z,3Z)-Cyclohepta-1,3-diene (3.54 g, 37.6 mmol) was dissolved in methylene chloride (36 mL) in a flask equipped with a dropping funnel under nitrogen. Tetrabutylammonium periodate (16.29 g, 37.6 mmol) was added and the reaction was cooled to 0° C. The dropping funnel was charged with tert-butyl hydroxycarbamate (5.01 g, 37.6 mmol) in methanol (30 mL). The contents of the funnel were added dropwise and stirring continued for 3 hours. The reaction was diluted with methylene chloride and transferred to a separatory funnel. The methylene chloride solution was washed sequentially with water and brine. The organic phase was then dried over magnesium sulfate. Filtration and evaporation provided the crude product. The material was purified on a 330 g ISCO silica gel column (0-70% ethyl acetate in hexanes). Evaporation of the product-containing fractions gave 23A (5.44 g, 64% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.40 (ddd, 1H, J=9.2, 6.9, 0.8 Hz), 6.18 (ddd, 1H, J=9.1, 6.1, 1.1 Hz); 4.60-4.73 (m, 2H); 1.53-1.87 (m, 4H); 1.46 (dtt, 1H, J=14.1, 4.9, 4.9, 2.4, 2.4 Hz); 1.39 (s, 9H); 1.24 (qd, 1H, J=12.9, 6.0 Hz).

1. customequipped with a dropping funnel under nitrogen
2. additionThe contents of the funnel were added dropwise
3. customtransferred to a separatory funnel
4. washThe methylene chloride solution was washed sequentially with water and brine
5. dry with materialThe organic phase was then dried over magnesium sulfate
6. filtrationFiltration and evaporation
7. customprovided the crude product
8. customThe material was purified on a 330 g ISCO silica gel column (0-70% ethyl acetate in hexanes)
9. customEvaporation of the product-containing fractions

ORD record

ord-2c39c7796300468f81a7ed88fce287ab

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791257B2