反应详情

Charge an oven-dried round bottom flask with (R)-3-methoxy-4-(3-triisopropylsilanyloxy-pyrrolidin-1-yl)-phenylamine (750 mg, 2.05 mmol), purge with nitrogen, and dilute with CH2Cl2 (11 mL). Add trimethylaluminum (2M in hexanes, 1.03 mL, 2.05 mmol) dropwise by syringe and stir 20 min at room temperature. Add solid 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (364 mg, 1.37 mmol) to the reaction mixture and stir overnight at ambient temperature. Absorb the reaction mixture on silica gel and purify by silica gel flash chromatography, using a gradient of EtOAc/hexane (0-100%) to give the title compound (1.02 g, 73%). MS (ES+) 630.1 (M+1)+. 1H NMR (CDCl3): δ 9.88 (bs, 1H), 7.82 (d, J=8.8 Hz, 2H), 7.48 (bs, 1H), 7.37 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.4 Hz, 1H), 6.69 (bs, 1H), 4.60-4.52 (m, 1H), 4.19-4.11 (m, 2H), 3.81 (s, 3H), 3.69-3.58 (m, 1H), 3.39-3.29 (m, 1H), 3.26 (t, J=5.3 Hz, 2H), 3.20-3.02 (m, 2H), 2.21-2.08 (m, 1H), 1.93-1.83 (m, 1H), 1.59 (bs, 1H), 1.12-0.95 (m, 21H).

1. custompurge with nitrogen
2. additiondilute with CH2Cl2 (11 mL)
3. customAbsorb the reaction mixture on silica gel
4. custompurify by silica gel flash chromatography