3-Fluorobenzoic Acid → 2-(Benzyloxy)-5-[(3-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

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Reaction Steps

2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.159 g, 0.42 mmol) was added to a stirred solution of 3-fluorobenzoic acid (0.059 g, 0.42 mmol) in DMF (2.0 mL) at 0° C. The reaction mixture was stirred for 5 minutes and then DIPEA (0.08 mL, 0.45 mmol) and 2-(benzyloxy)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (0.08 g, 0.35 mmol) were added. The mixture was stirred at room temperature for 16 hours, diluted with a saturated solution of NH4Cl and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo to yield 2-(benzyloxy)-5-[(3-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (0.055 g, 45% yield) as a white solid. C20H18FN3O2. 1H NMR (mixture of conformers 1/1; 500 MHz, CDCl3) δ ppm 3.87 (br. s., 1 H), 4.09 (br. s., 2 H), 4.20 (br. s., 1 H), 4.62 (br. s., 1 H), 4.84 (br. s., 1 H), 5.18 (s, 2 H), 5.44 (br. s., 0.5 H), 5.56 (br. s., 0.5 H), 7.14-7.21 (m, 2 H), 7.23 (dt, J=7.8, 1.2 Hz, 1 H), 7.29-7.34 (m, 1 H), 7.37 (t, J=7.4 Hz, 2 H), 7.40-7.47 (m, 3 H).

Provenance & Evidence