(1S,2S,5R,6S) -2-tert-Butoxycarbonylamino-bicyclo [3.1.0] hexane-2,6-dicarboxylic acid

Synthesis of (1S,2S,5R,6S) -2-tert-Butoxycarbonylamino-bicyclo [3.1.0] hexane-2,6-dicarboxylic acid

 A 1 L flask was charged with (1S,2S,5R,6S)-2-amino-bicyclo [3.1.0]hexane-2,6-dicarboxylic acid monohydrate (24.4 g, 0.12 mol, 1 equiv), dioxane (200 mL) and di-tert-butyl dicarbonate (52.4 g, 0.24 mol, 2.0 equiv). The suspension was vigorously stirred while sodium hydroxide 1N (420 mL, 3.5 equiv) was added. The mixture was stirred for 2 days, then 2.0 more equiv of di-tert-butyl dicarbonate were added and the reaction stirred for 3 additional days at rt. After 5 total days of reaction, water (400 mL) was added to dissolve the salts. The aqueous layer was extracted with ethyl acetate (4×100 mL) to remove the excess of reagent, and then taken to ca. pH=2 using 6 N hydrochloric acid. The acidic aqueous phase was then extracted using ethyl ether (6×200 mL). The combined organic layers were washed with water (250 mL) and brine (250 mL). After drying over sodium sulfate, solvents were evaporated in vacuum to afford a foamy white solid (26.4 g).

77% Yield. 

http://www.google.im/patents/US20040138304?cl=un

mp 100-101° C. 

[α]_D ²⁵=−41.1° (c=1.0, MeOH). 

¹H NMR (Methanol-d₄) δ: 4.98 (brs, 1H), 2.44 (dd, 1H, J=6.2, 2.6 Hz), 2.19-1.92 (m, 4H), 1.62 (t, 1H, J=2.8 Hz), 1.43 (s, 9H), 1.29 (m, 1H). 

¹³C NMR (Methanol-d₄) δ: 175.6, 175.2, 158.2, 60.1, 34.6, 31.9, 28.4, 27.2, 25.6, 20.6. MS (Neg. Electrospray): 284.2 (M⁺−H).