反应详情

To a solution of 1-tert-butyl 4-((1R,3 aS,5aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl) 2,2-dimethylsuccinate (55.2 mg, 0.070 mmol) in DCM (1 mL) was added TFA (0.3 ml, 3.89 mmol). The reaction mixture was stirred rt and turned purple/red. After 1 h, TLC (95:5 DCM:MeOH) showed the reaction was completed. The reaction mixture was diluted with DCE (2 mL) and concentrated to a red solid. The crude material was redissolved in DCM (0.5 mL). Et2O was added to produce ad precipitate which was filtered and washed with Et2O to give 4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid as off-white solid (9.5 mg, 18.8% yield). LC/MS: m/e 729.5 (M+H)+, 3.49 min (method 8). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.79 (br. s., 1H), 4.68 (s, 1H), 4.54-4.43 (m, 1H), 4.23 (br. s., 1H), 3.58 (br. s., 1H), 3.49-3.31 (m, 2H), 3.29-3.13 (m, 3H), 3.11-2.91 (m, 4H), 2.79 (br. s., 1H), 2.72-2.64 (m, 1H), 2.59 (s, 1H), 2.56 (d, J=6.4 Hz, 1H), 2.39 (d, J=11.5 Hz, 1H), 2.28 (br. s., 1H), 1.93 (br. s., 4H), 1.70 (s, 3H), 1.69-1.49 (m, 9H), 1.48-1.40 (m, 3H), 1.35 (br. s., 2H), 1.31 (br. s., 3H), 1.30 (br. s., 3H), 1.09 (br. s., 3H), 1.03 (s, 3H), 1.00-0.89 (m, 2H), 0.86 (br. s., 3H), 0.85 (s, 3H), 0.83 (s, 3H), 0.79-0.73 (m, 1H)

1. concentrationconcentrated to a red solid
2. dissolutionThe crude material was redissolved in DCM (0.5 mL)
3. additionEt2O was added
4. customto produce ad precipitate which
5. filtrationwas filtered
6. washwashed with Et2O