反应详情

温度

55 °C

Pyridinium para-toluene sulfonate (44.0 mg, 0.17 mmol) was added to Intermediate 4c (124 mg, 0.17 mmol) in MeOH (3.0 mL). After 2 h, further pyridinium para-toluene sulfonate (100 mg, 0.39 mmol) was added, and the reaction stirred for 12 h. The reaction was then heated to 55° C. for 2 h, then cooled, and the solvent volume reduced to approximately ⅓ of its volume in vacuo. The residue was partitioned between EtOAc (50 mL) and saturated NaHCO3 (50 mL). The aqueous layer was extracted into EtOAc (3×), then the combined organic layers washed with brine, dried (MgSO4) and evaporated in vacuo. The product was purified by FCC, using 0-10% MeOH in DCM, then further purified by HPLC (C18 X-select column, 10-98% MeCN in H2O, 0.1% formic acid) to give the title compound (50.0 mg, 0.08 mmol, 47%). LCMS (Method 5): Rt 4.04 mins, m/z 624 [MH+]. 1H NMR (400 MHz, CDCl3): 1.30 (9H, s), 1.40-1.44 (3H, d, J=6.9 Hz), 1.44-1.47 (3H, d, J=6.9 Hz), 1.84-1.98 (1H, m), 2.00-2.10 (2H, m), 2.18-2.26 (1H, m), 3.16-3.26 (1H, sp, J=6.9 Hz), 3.87-3.92 (2H, m), 4.03-4.07 (2H, m), 5.01-5.09 (1H, td, J 8.9, 5.3 Hz), 5.14-5.17 (1H, t, J=4.0 Hz), 5.47-5.52 (1H, br d, J=8.7 Hz), 6.29 (1H, s) 6.60 (1H, br s), 6.80-6.84 (1H, m), 6.96-7.00 (1H, dd, J 9.9, 2.1 Hz), 7.07-7.11 (2H, m), 7.23-7.30 (5H, m), 7.38-7.40 (1H, d, J=1.6 Hz), 7.53-7.57 (1H, d, J=9.9 Hz).

1. temperaturecooled
2. customThe residue was partitioned between EtOAc (50 mL) and saturated NaHCO3 (50 mL)
3. extractionThe aqueous layer was extracted into EtOAc (3×)
4. washthe combined organic layers washed with brine
5. dry with materialdried (MgSO4)
6. customevaporated in vacuo
7. customThe product was purified by FCC
8. customfurther purified by HPLC (C18 X-select column, 10-98% MeCN in H2O, 0.1% formic acid)