反应详情

温度

85 °C

Argon was bubbled through a solution of tert-butyl (2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)-3-pyridinyl]ethyl{[(2R)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-chromen-2-yl]methyl}carbamate (Example 370, 395 mg, 0.55 mmol) in toluene (15 mL) and 1,4-dioxane (3 mL) for 10 minutes. Bis(diphenylphosphino)ferrocene-palladium (40 mg) and methyl 4-iodobenzoate (216 mg, 0.83 mmol) were added, and bubbling with argon was continued for another 5 minutes. 2 N aq. sodium carbonate solution (3 mL, 6 mmol) was added and the reaction mixture was heated (85° C.) for 16 hours. After cooling, the mixture was filtered through a pad of silica gel and Celite® using ethyl acetate to rinse. The filtrate was concentrated in vacuo and then flash chromatography of the residue over silica gel using 20% ethyl acetate/hexanes afforded 276 mg (69%) of the desired product. The product had: 1H NMR (CDCl3, δ): 8.65 (d, J=20.0 Hz, 1 H), 8.13 (d, J=7.9 Hz, 2 H), 7.91 (dd, J=16.8, 8.1 Hz, 1 H), 7.67 (d, J=7.6 Hz, 2 H), 7.24-7.47 (m, 3 H), 6.93 (dd, J=8.1, 1.8 Hz, 1 H), 5.98 (d, J=3.9 Hz, 1 H), 5.23 (dd, J=43.5, 5.5 Hz, 1 H), 4.21-4.43 (m, 1 H), 4.00 (s, 3 H), 3.37-3.95 (m, 4 H), 2.84-3.09 (m, 2 H), 2.22 (s, 3 H), 2.20 (s, 3 H), 2.03-2.18 (m, 1 H), 1.74-1.91 (m, 1 H), 1.59 (d, J=10.4 Hz, 9 H), 0.99 (s, 9 H), 0.17 (s, 3 H), 0.00 (s, 3 H); mass spectroscopy gave m/z=726.4 [M+H]+ (calc'd exact mass for C42H55N3O6Si=725.4).

1. custombubbling with argon
2. temperatureAfter cooling
3. filtrationthe mixture was filtered through a pad of silica gel and Celite®
4. washto rinse
5. concentrationThe filtrate was concentrated in vacuo