Acetic Acid → HCID 11315931, compound

Participants

Reaction Steps

Pd(II)(PhCN)2Cl2 (15 mg, 0.039 mmol) and CuI (9 mg, 0.047 mmol) were dissolved in anhydrous dioxane (3 mL), 10 wt % P(t-Bu)3 in hexanes (0.200 mL, 13.6 mg, 0.067 mmol), NH(i-Pr)2, (0.085 mL, 0.60 mmol), 4-[6-(4-bromo-2-fluoro-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (243 mg, 0.50 mmol), and TMS-acetylene (0.083 mL, 0.60 mmol), were added and the reaction mixture was sealed, purged with nitrogen, and stirred at room temperature for 12 h. The reaction mixture was diluted with EtOAc (15 mL), the mixture was filtered through a silica pad, the solvent was evaporated in vacuo at 23 C to give a dark oil which was dissolved in THF (3.5 mL) and MeOH (1.5 mL). 1.0 N NaOH (0.75 mL, 0.75 mmol) was added and after 5 min glacial AcOH (0.086 mL, 1.5 mmol) was added. After addition of silica (2.4 g) the solvent was evaporated in vacuo at 25 C to give a solid which was pulverized with mortar and pestle. This crude product was adsorbed onto silica and purified by flash chromatography using hexanes-EtOAc, 82:18, then hexanes-EtOAc, 75:25, v/v, to give the title Compound C240 as a resin (67 mg, 32% over 2 steps). 1H NMR (400 MHz, CDCl3) δ 1.25 (d, J=6 Hz, 6H), 1.78 (m, 2H), 1.98 (m, 2H), 2.17 (s, 3H), 3.07 (s, 1H), 3.40 (m, 2H), 3.74 (m, 2H), 4.92 (m, 1H), 5.32 (m, 1H), 7.14 (m, 1H), 7.29 (m, 2H), 8.18 (s, 1H). LRMS calculated for C22H24FN3O4: 413.18. Found: 414.5 (M+H).

Provenance & Evidence