ETHYL 2-(2H-1,2,3,4-TETRAAZOL-5-YL)ACETATE

General procedure: The mixture of organic nitrile (1 mmol), NaN3 (1.25 mmol) and L-proline (30 molpercent) in DMF (5mL) was stirred at 110 °C for 1-2 h. The progress of the reaction was monitored by TLC. Aftercompletion of the reaction, the reaction mixture was allowed to cool to room temperature. Thecooled reaction mixture was poured in ice water (15 mL) with stirring. The resulting mixture wasacidified with dilute HCl under vigorous stirring. The solid product* was filtered under suction, washed with sufficient cold water till free of acid. The product was air dried to obtain the pureproduct.*In cases where solid product was not obtained after acidification, like benzyl cyanide andaliphatic nitriles, the acidified aqueous phase was extracted with ethyl acetate (2 X 20 mL), thecombined organic phase was washed with brine, dried over anhydrous sodium sulfate andconcentrated in vacuo to get the corresponding pure product.[00772] Intermediate 84a: ethyl 2-(IH-tetrazol-5-yI)acetate[00773] A stirred solution of ethyl cyanoacetate (0.94mL, 8.84mmol), sodium azide (603mg, 9.28mmol) and ammonium chloride (497mg, 9.28mmol) in DMF (8.9mL) was heated at 100 °C overnight. The mixture was then allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in water (4mL) and acidified with SM HCI(aq) then extracted with EtOAc (3 x 1 OmL). The combined organic layers were washed with brine (1 SmL), dried overNa2504, filtered and concentrated in vacuo. The residue was dissolved in a small amount of EtOAc and heptane was added causing a solid to crash out. The mixture was filtered and the precipitate collected and dried to give ethyl 2-(1H-tetrazol-S-yl)acetate (898mg, S.74mmol, 65percent) as a tan solid. 1H NMR (DMSO-d6, 400MHz) O/ppm: 4.16 (2H, 5), 4.15 (2H, q, J= 7.2Hz), 1.21 (3H, t, J= 7.2Hz), exchangeable acid proton not seen.MS Method 3: RT: 2.68 mi m/z 157.2 [M+H].General procedure: The mixture of organic nitrile (1 mmol), NaN3 (1.25 mmol) and L-proline (30 mol%) in DMF (5mL) was stirred at 110 C for 1-2 h. The progress of the reaction was monitored by TLC. Aftercompletion of the reaction, the reaction mixture was allowed to cool to room temperature. Thecooled reaction mixture was poured in ice water (15 mL) with stirring. The resulting mixture wasacidified with dilute HCl under vigorous stirring. The solid product* was filtered under suction, washed with sufficient cold water till free of acid. The product was air dried to obtain the pureproduct.*In cases where solid product was not obtained after acidification, like benzyl cyanide andaliphatic nitriles, the acidified aqueous phase was extracted with ethyl acetate (2 X 20 mL), thecombined organic phase was washed with brine, dried over anhydrous sodium sulfate andconcentrated in vacuo to get the corresponding pure product.[00772] Intermediate 84a: ethyl 2-(IH-tetrazol-5-yI)acetate[00773] A stirred solution of ethyl cyanoacetate (0.94mL, 8.84mmol), sodium azide (603mg, 9.28mmol) and ammonium chloride (497mg, 9.28mmol) in DMF (8.9mL) was heated at 100 C overnight. The mixture was then allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in water (4mL) and acidified with SM HCI(aq) then extracted with EtOAc (3 x 1 OmL). The combined organic layers were washed with brine (1 SmL), dried overNa2504, filtered and concentrated in vacuo. The residue was dissolved in a small amount of EtOAc and heptane was added causing a solid to crash out. The mixture was filtered and the precipitate collected and dried to give ethyl 2-(1H-tetrazol-S-yl)acetate (898mg, S.74mmol, 65%) as a tan solid. 1H NMR (DMSO-d6, 400MHz) O/ppm: 4.16 (2H, 5), 4.15 (2H, q, J= 7.2Hz), 1.21 (3H, t, J= 7.2Hz), exchangeable acid proton not seen.MS Method 3: RT: 2.68 mi m/z 157.2 [M+H].A solution of ethyl cyanoacetate (1 mL, 9.4 mmol), triethylammonium chloride (1.56 g, 11.27 mmol), and sodium azide (0.73 g, 11.27 mmol) in toluene (50 mL) was heated to 100 C for 16 h. The obtained orange solution with some off-white precipitate was allowed to cool to ambient temperature and the solvent was removed under vacuum in a rotary evaporator. The orange residue was dissolved in water and acidified with 3 M hydrochloric acidsolution to pH 2. The precipitated solid was filtered and purified by crystallization from hexane-EtOAc mixture. Mp: 124-126 C

Molecular Weight:156.14
XLogP3:-0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:4
Exact Mass:156.06472551
Monoisotopic Mass:156.06472551
Topological Polar Surface Area:80.8
Heavy Atom Count:11
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes