Reaction Steps
A solution of methyl(2S)-2-(tert-butoxy)-2-[(22S)-5,8-dibromo-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate (150 mg, 0.184 mmol, 1 equiv), SPhos (15 mg, 0.037 mmol, 0.2 equiv), Pd(OAc)2 (8 mg, 0.037 mmol, 0.2 equiv), n-BuOH (0.055 mL, 0.74 mmol, 4 equiv), and Cs2CO3 (90 mg, 0.276 mmol, 1.5 equiv) in 10:1 DMF:water (3.6 mL) was heated to 80° C. for 2 h. More Pd(OAc)2 (41 mg) was added and the reaction was stirred for 3 h. The reaction was then removed from heat and stirred at ambient temperature for 4 d. More Pd(OAc)2 (10 mg) was heated to 85° C. for 5 h. The reaction was then removed from heat. Upon cooling to ambient temperature, the reaction was diluted with EtOAc and washed with water. The EtOAc was dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (63 mg, 47%). 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J=8.0 Hz, 1H), 8.11 (d, J=6.8 Hz, 2H), 7.54 (t, J=7.7 Hz, 1H), 7.31 (d, J=7.8 Hz, 1H), 7.11 (dd, J=9.0, 3.0 Hz, 1H), 7.03-6.90 (m, 2H), 6.15 (br. s., 1H), 4.47 (d, J=6.3 Hz, 1H), 3.95 (t, J=11.2 Hz, 1H), 3.80-3.66 (m, 5H), 3.57-3.42 (m, 2H), 3.09 (d, J=11.3 Hz, 1H), 2.71 (d, J=11.8 Hz, 1H), 2.57 (s, 3H), 2.01-1.66 (m, 10H), 1.28 (s, 3H), 1.24 (s, 9H), 1.11 (d, J=6.0 Hz, 3H). LCMS (ESI, M+1): 736.20.
