Reaktion #172791

Reaktionsgleichung

methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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

lithium hydroxide monohydrate

→

4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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)benzoic acid

Ausbeute 38.8%

Lösungsmittel

THF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe reaction mixture was concentrated
2. 2
   workup.DISSOLUTIONThe residue was redissolved in THF/MeOH
3. 3
   workup.ADDITIONsilica gel (2 g) was added
4. 4
   Einengenthe mixture was concentrated to dryness
5. 5
   Wascheneluted with 0% B (solvent B=(90:10 DCM

Vorschrift

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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 (101 mg, 0.139 mmol) in THF (5 mL) was added a solution of lithium hydroxide monohydrate (17.49 mg, 0.417 mmol) in water (1.000 mL). The resulting mixture was stirred at 75° C. After 18 h, the reaction mixture was concentrated. The residue was redissolved in THF/MeOH, silica gel (2 g) was added and the mixture was concentrated to dryness. The absorbed material was loaded onto a silica gel column (25 g cartridge) and eluted with 0% B (solvent B=(90:10 DCM:MeOH, A=100% DCM) to 50% B for 180 mL, then hold at 50% B for 900 mL. Thus was obtained 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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)benzoic acid (39 mg, 0.054 mmol, 38.6% yield) as white solid. LCMS: m/e 713.6 (M+H)+, 2.32 min (method 1). 1H NMR (500 MHz, 1:1 CDCl3:METHANOL-d4) δ 7.92 (d, J=8.2 Hz, 2H), 7.20 (d, J=8.2 Hz, 3H), 6.62 (br. s., 1H), 5.33-5.24 (m, 1H), 4.72 (s, 1H), 4.63 (s, 1H), 2.61-2.36 (m, 3H), 2.13 (dd, J=17.2, 6.3 Hz, 1H), 2.04-1.95 (m, 1H), 1.73 (br. s., 1H), 1.71 (s, 3H), 1.41 (d, J=6.1 Hz, 2H), 1.26 (br. s., 9H), 1.15 (s, 3H), 1.10 (br. s., 1H), 1.03 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H), 0.88 (d, J=6.7 Hz, 2H), 0.86-0.83 (m, 2H).

Quelle