反応 #172878

反応方程式

methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-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)-2-fluorobenzoate

3-(2-oxopyrrolidin-1-yl)propyl trifluoromethanesulfonate

potassium iodide

phosphoric acid

potassium

→

methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(3-(2-oxopyrrolidin-1-yl)propylamino)-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

収率 26.2%

溶媒

—

crude solution

acetonitrile

反応条件

後処理

1. 1
   その他prepared above) (1.0 mL, 0.384 mmol)
2. 2
   workup.ADDITIONwas added
3. 3
   その他The mixture was flushed with N2
4. 4
   その他the vial was sealed
5. 5
   温度After 15.5 h of heating
6. 6
   温度the mixture was cooled to rt
7. 7
   workup.ADDITIONAn additional 0.5 mL of the above crude solution containing the triflate
8. 8
   workup.ADDITIONwas added
9. 9
   温度the mixture was again heated to 120° C
10. 10
    温度After heating the mixture for an additional 70.25 h
11. 11
    温度the mixture was cooled to rt
12. 12
    その他was purified by flash chromatography
13. 13
    workup.ADDITIONThe fractions containing the expected product
14. 14
    濃縮concentrated under reduced pressure

実験手順

To a sealable flask containing methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-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)-2-fluorobenzoate (50 mg, 0.089 mmol) was added potassium iodide (39.9 mg, 0.240 mmol) and phosphoric acid, potassium salt (83 mg, 0.392 mmol). The mixture was diluted with acetonitrile (1 mL) and 3-(2-oxopyrrolidin-1-yl)propyl trifluoromethanesulfonate (the crude solution prepared above) (1.0 mL, 0.384 mmol) was added. The mixture was flushed with N2, then the vial was sealed and heated to 120° C. After 15.5 h of heating, the mixture was cooled to rt. An additional 0.5 mL of the above crude solution containing the triflate was added and the mixture was again heated to 120° C. After heating the mixture for an additional 70.25 h, the mixture was cooled to rt. The mixture was adsorbed to silica gel and was purified by flash chromatography using a 0-5% MeOH in DCM gradient and a Thomson 12 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(3-(2-oxopyrrolidin-1-yl)propylamino)-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 (16 mg, 0.023 mmol, 26.2% yield) as a yellow film. LCMS: m/e 687.5 (M+H)+, 2.04 min (method 2).

出典