(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).

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

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

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

[0123] (1S,2S,5R,6S)-2-Amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid (15.0 g, 73.9 mmol) was slowly dissolved in 250 mL of saturated sodium bicarbonate. After complete solution, dioxane (100 mL) and allyl chloroformate (15.7 mL, 147.8 mmol) were added at room temperature and the mixture was stirred overnight. The reaction mixture was diluted with water (100 mL) and washed with three portions of ethyl acetate. The organic layer was extracted once with saturated sodium bicarbonate. The combined aqueous layers were acidified to pH 1 with 4N hydrochloric acid and extracted with two portions of ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated to provide the title compound as an oil (13.4 g, 67% yield).

¹H-NMR (CD₃OD)

δ: 6.01-5.82 (m, 1 H); 5.35-5.13 (m, 2 H); 4.51 (d, J=5.1 Hz, 2 H); 2.48-1.78 (m, 5 H); 1.69-1.62 (m, 1 H); 1.45-1.29 (m, 1 H).

 ¹³C-NMR (CD₃OD)δ: 176.7, 176.6, 158.3, 134.2, 117.4, 67.3, 66.3, 35.8, 33.1, 29.9, 27.0, 22.0.