Triethylamine → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-isocyanato-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

温度

100 °C

To a slurry of (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(methoxycarbonyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (10 g, 17.46 mmol) in 1,4-dioxane (200 mL) was added triethylamine (4.38 mL, 31.4 mmol) followed by diphenyl phosphoryl azide (5.82 mL, 26.2 mmol). The resulting white slurry was heated to 100° C. After 5 h, the reaction was allowed to cool to rt and was then diluted with EtOAc and washed with 1N NaOH (2×70 mL). The combined aqueous layer was extracted with EtOAc (2×150 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated to a slurry (75 mL) which was stored in a refrigerator overnight. The slurry was filtered and the white solid product was washed with Et2O. The liquid filtrate was concentrated to a yellow slurry which was filtered and washed with Et2O to give more white solid product. The two batches of white solid were combined and dried in vacuo to give the title compound (8.6 g, 15.09 mmol, 86% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.0 (2H, d, J=8.2 Hz), 7.2 (2H, d, J=8.2 Hz), 5.3 (1H, d, J=4.6 Hz), 4.8 (1H, s), 4.7 (1H, s), 3.9 (3H, s), 2.6 (1H, td, J=10.8, 5.8 Hz), 2.1-2.2 (2H, m), 1.8-2.0 (4H, m), 1.7-1.8 (1H, m), 1.7 (3H, s), 1.5-1.7 (5H, m), 1.4-1.5 (5H, m), 1.3-1.4 (2H, m), 1.2-1.3 (2H, m), 1.1 (3H, s), 1.1-1.1 (1H, m), 1.0 (3H, s), 1.0 (3H, s), 1.0 (3H, br. s.), 1.0 (3H, br. s.). 13C NMR (CHLOROFORM-d) δ ppm 14.2, 15.4, 16.2, 19.2, 19.5, 20.8, 21.0, 24.7, 27.4, 29.0, 29.2, 33.3, 36.0, 37.2, 39.0, 39.0, 40.3, 41.5, 41.8, 47.8, 49.0, 49.2, 51.7, 52.6, 66.8, 71.3, 110.2, 121.3, 123.7, 127.6, 128.2, 129.8, 146.0, 148.4, 148.6, 166.9.

1. temperatureto cool to rt
2. washwashed with 1N NaOH (2×70 mL)
3. extractionThe combined aqueous layer was extracted with EtOAc (2×150 mL)
4. dry with materialThe combined organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated to a slurry (75 mL) which
7. customwas stored in a refrigerator overnight
8. filtrationThe slurry was filtered
9. washthe white solid product was washed with Et2O
10. concentrationThe liquid filtrate was concentrated to a yellow slurry which
11. filtrationwas filtered
12. washwashed with Et2O
13. customto give more white solid product
14. customdried in vacuo

ORDレコード

ord-8bdbfed2ed894cd9b6548729fbe31ad3

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08846647B2