Amino-Hepta-5,6-Dienoic Acid and Intermediates Thereof

Patent (S)-4-Amino-Hepta-5,6-Dienoic Acid and Intermediates Thereof 

Assignee Merrell Pharmaceuticals Utility Irreversible GABA-T Inhibitor 

The product from Step 1 (0.44 mmol) was dissolved in 2 ml THE, cooled to —78°C, 1M lithium triethylborohydride (0.66 mmol in THE) added at such a rate the temperature did not exceed — 66°C, and the mixture stirred 1 hour after the addition was completed. The reaction was quenched using NaHC03 solution, extracted with EtOAc and purified as in Step 1 to give a 7 3 mixture of diasteromers at the 5 position. 

Trifluoroacetic acid (15.6 mmol) was added dropwise to the stereo-isomers from Step 2 (7.29 mmol) dissolved in CH2CI2, stirred for 2 hours, and then treated with water. The 

The product from Step 3 (0.89mmol) and 4ml 1 M HCl were heated to 90°C 18 hours, cooled, and neutralized with 1 M NaOH solution. The product mixture was purified by ion exchange chromatography using Dowex 1X2, 100 mesh, hydroxide form using 0.25 M acetic acid, to give 0.1 g of product, mp = 135 °C. 

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