反应详情

A 3.10 g (13.2 mmol) sample of 6-iodo-2-picoline-5-ol (Aldrich Chem. Co.) was dissolved in 5 mL of DMF, and (Ph3P)2PdCl2 (0.38 g, 0.50 mmol), CuI (0.377 g, 1.98 mmol) and triethylamine (1.80 mL, 13.2 mmol) were added. The mixture was stirred under N2 at room temperature for 1 hour, then 2.15 g (11 mmol) of 1-BOC-2-(S)-ethynylpyrrolidine, from Example 1c above, dissolved in 1 mL of DMF, was added carefully. The reaction was stirred at 60° C. for 16 hours, then cooled to room temperature. The reaction mixture was diluted with 2 N HCl and extracted with ether. The aqueous layer was adjusted to pH 10 with K2CO3, then extracted with CH2Cl2. The extract was washed with 20% NaOH, brine, dried over MgSO4, and the solvent was removed. The residue was repeatedly dissolved in toluene and distilled to azeotropically remove the DMF. The residue was chromatographed on silica gel, eluting with 100:0 to 50:50 hexane:EtOAc to give 521 mg of title compound: 1H NMR (CDCl3, 300 MHz) δ 1.33 and 1.47 (2 s, 9H), 1.90-2.30 (m, 4H), 2.63 (s, 3H), 3.45-3.65 (m, 2H), 4.95 and 5.10 (2 s, 1H), 5.58 (s, 1H), 7.02 (d, 1H), 7.55 (d, 1H); MS m/z: 303 (M+H)+.

1. additionwas added carefully
2. stirringThe reaction was stirred at 60° C. for 16 hours
3. temperaturecooled to room temperature
4. extractionextracted with ether
5. extractionextracted with CH2Cl2
6. washThe extract was washed with 20% NaOH, brine
7. dry with materialdried over MgSO4
8. customthe solvent was removed
9. dissolutionThe residue was repeatedly dissolved in toluene
10. distillationdistilled
11. customto azeotropically remove the DMF
12. customThe residue was chromatographed on silica gel
13. washeluting with 100:0 to 50:50 hexane