Ethyl 1H-1,2,3-triazole-5-carboxylate

On a Vapourtec R2+/R4 flow system equipped with three PTFA reactor coils (a 10 mL) and a 250 psi back pressure regulator, ethyl propiolate and trimethylsilyl azide were injected via 2 mL loops. The flow rate was set to 0.5 mL/min, with a residence time of 1.5 h. The system was heated to 140 °C. Injections were performed every 40 min. The solvent used was acetonitrile. The total mixture coming out of the reactor was collected. In total, 5 injections were performed. The mixture was collected, and acetonitrile removed in vacuo (the collector of the rotary evaporator was filled with sat. aq. NaHC0A solution of ethyl lH-l, 2, 3-triazole-5-carboxylate (example 23a; 300 mg, 2.13 mmol, Eq: 1) in toluene (15 ml) was treated with cyclobutanol (230 mg, 250 mu, 3.19 mmol, Eq: 1.5) and 2-(tributylphosphoranylidene)acetonitrile (1.03 g, 1.11 ml, 4.25 mmol, Eq: 2), under Ar. The mixture was stirred for lh30 at 80 °C, before being diluted with EtOAc. The organic phase was washed with water (lx) and brine (2x), dried over Na2S04, filtered, and evaporated. MPLC (Si02; heptane/EtOAc, gradient from 100:0 to 70:30 within 30 min) gave the title compound (142 mg, 33.9percent) as a colorless oil. MS (ESI): m/z = 196.1 (0393) [M+H]+.A solution of ethyl lH-l, 2, 3-triazole-5-carboxylate (example 23a; 500 mg, 3.54 mmol, Eq: 1) in TFA (4.44 g, 3 ml, 39 mmol, Eq: 11) was treated with 2-methylpropan-2-ol (525 mg, 673 mu, 7.09 mmol, Eq: 2) and H2S04 (347 mg, 189 mu, 3.54 mmol, Eq: 1), at 25 °C. The resulting mixture was stirred for 5h at this temperature, before being partitioned between H20 and EtOAc. The organic phase was washed with sat. NaHCOs, brine, dried over Na2S04, filtered, and evaporated. MPLC (Si02; heptane/EtOAc, gradient from 100:0 to 50:50 within 30 min) gave the title compound (313 mg, 45percent) as a colorless oil. MS (ESI): m/z = 198.1 [M+H]+.A solution of ethyl lH-l, 2, 3-triazole-5-carboxylate (example 23a; 500 mg, 3.54 mmol, Eq: 1) and (4-bromophenyl)boronic acid (1.07 g, 5.31 mmol, Eq: 1.5) in CH2C12 (30 mL) was treated with copper (II) acetate (322 mg, 1.77 mmol, Eq: 0.5) and KotBu (596 mg, 5.31 mmol, Eq: 1.5), at 25 °C under Air. The mixture was stirred at this temperature for 72h, before being diluted with CH2C12. The organic phase was washed with water (lx), dried over Na2S04, filtered and evaporated. MPLC (Si02; heptane/EtOAc, gradient from 100:0 to 0: 100 within 40 min) gave the title compound (82 mg, 8percent) as a white solid. MS (ESI): m/z = 298.0 [M+H]+.