反应详情

A solution of (3-chloropyrazin-2-yl)-methanol (47 g, 0.33 mol), isoindole-1,3-dione (58.3 g, 0.396 mol, 1.2 eq.), and triphenylphosphine (89.7 g, 0.396 mol, 1.2 eq.) in anhydrous THF (1.5 L) was charged with DIAD (80.2 g, 0.396 mol, 77.1 mL, 1.2 eq.) dropwise at rt, under N2, making sure the internal temperature did not surpass 40° C. The crude material was adsorbed onto silica gel, dry loaded, and purified by chromatography on silica gel [6″×16″ column, 2.75 kg silica gel, eluting with Hex:CH2Cl2 1:1→neat CH2Cl2→MeCN:CH2Cl2 2→10%.] Material was combined and concentrated in vacuo. Residue was dissolved as best as possible in hot CH2Cl2 (500 mL), after which i-PrOH was added and a white crystalline solid began to precipitate out of solution. Solid was filtered, washed with i-PrOH, and oven-dried to remove all traces of solvent, affording the title compound, as an off-white solid; 1H NMR (400 MHz, CDCl3) δ 5.10 (s, 1H), 7.75-7.80 (m, 2H), 7.89-7.94 (m, 2H), 8.26 (1H, d, J=2.45 Hz), 8.31 (1H, d, J=2.49 Hz); MS (ES+): m/z 274.21/276.19 (100/50) [MH+]; HPLC: tR=3.35 min (OpenLynx, nonpolar—7 min).

1. customdid not surpass 40° C
2. customdry loaded
3. custompurified by chromatography on silica gel [6″×16″ column, 2.75 kg silica gel
4. washeluting with Hex
5. concentrationconcentrated in vacuo
6. dissolutionResidue was dissolved as best as possible in hot CH2Cl2 (500 mL)
7. additionafter which i-PrOH was added
8. customto precipitate out of solution
9. filtrationSolid was filtered
10. washwashed with i-PrOH
11. customoven-dried
12. customto remove all traces of solvent