Hydrochloric Acid → 3-[[(1,1-Dimethylethoxy)carbonyl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid

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Reaction Steps

Combine 4-Oxo-3-aza-tricyclo[4.2.1.0(2,5)]non-7-ene-3-carboxylic acid tert-butyl ester (60.94 g, 0.2590 mol;) and Tetrahydrofuran (800 mL, 10 mol;) in 2 L Ehrlenmeyer flask. Addition of 1.00 M of Lithium hydroxide in Water (780 mL) gave a slight exotherm and the flask was cooled during addition of LiOH solution with an ice water bath. The mixture was then warmed to rt following addition and stirred at room temperature overnight. Cooled 0° C. in ice/water bath. Added conc HCl to pH 2. A milky white liquid ensued. The THF was mostly removed by rotovap to give a precipitated solid in the water. This aqueous/solid mixture was diluted with 700 mL of CH2Cl2 and stirred for two hours during which the solid completely dissolved in the organic layer. The aqueous was further extracted with 400 mL of CH2Cl2 and the combined organics were dried (MgSO4), filtered and concentrated to give 3-tert-Butoxycarbonylamino-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid as an off-white solid, put on high vac at 40° C. to remove excess dichloromethane present in the solid sample. (60.40 g, 92%). 1H-NMR(CDCL3, 400 MHz): δ 12.0 (broad absorption, 1H) 6.97 (d, J=10.6 Hz, 1H), 6.20 (s, 1H); 3.96 (t, J=9.6 Hz, 1H), 2.99 (s, 1H), 2.74 (s, 1H), 2.60 (d, J=8.4 Hz, 1H), 2.09 (d, J=9.3 Hz, 1H), 1.66 (d, J=9.4 Hz, 1H), 1.47 (s, 9H).

Provenance & Evidence