Reaction Steps
Methyl (2S)-2-[(2-methylbutan-2-yl)oxy 1-24(228)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[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: To a stirred solution of methyl (2S)-2-hydroxy-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[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 (50 mg, 0.084 mmol) in DCM (2 mL) and tert-pentyl acetate (0.692 mL, 5.85 mmol) at rt was added 70 wt % perchloric acid (0.022 mL, 0.251 mmol). After 3 h, the reaction mixture was diluted with DCM (25 mL), carefully quenched with sat. NaHCO3 (5 mL), organic layer separated and washed with brine (10 mL), dried (Na2SO4), filtered and concentrated to give yellow liquid. This was purified by flash column chromatograpgy on silica gel column using (10-50% EtOAc/Hex as eluant) to afford the desired methyl (25)-2-[(2-methylbutan-2-yl)oxy]-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[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 (10 mg, 0.015 mmol, 17.90% yield) as viscous oil. 1H NMR (500 MHz, CDCl3) δ 7.82-7.76 (m, 1H), 7.50 (t, J=7.7 Hz, 1H), 7.39-7.34 (m, 1H), 7.18 (d, J=1.9 Hz, 1H), 7.13 (dd, J=8.5, 2.0 Hz, 1H), 6.92 (d, J=8.5 Hz, 1H), 6.90 (s, 1H), 5.90 (s, 1H), 4.66-4.59 (m, 1H), 4.58-4.52 (m, 1H), 3.84-3.79 (m, 1H), 3.77 (s, 3H), 3.50 (td, J=7.7, 3.1 Hz, 1H), 3.44-3.35 (m, 1H), 3.27 (d, J=12.3 Hz, 1H), 2.89 (d, J=11.3 Hz, 1H), 2.61 (s, 3H), 2.36 (s, 3H), 2.07-1.96 (m, 3H), 1.89-1.80 (m, 1H), 1.79-1.70 (m, 3H), 1.63-1.47 (m, 6H), 1.26 (s, 3H), 1.23 (s, 3H), 1.17 (d, J=6.0 Hz, 3H), 1.15 (s, 3H), 0.83 (t, J=7.5 Hz, 3H). LCMS (M+H)=669.4. 35 mg of starting material was also recovered.
