Sodium Hydroxide → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(cyclopropylmethylamino)-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

HRID 85640Notes

Reaction equation

HRID 85640 reaction equation
[CH:1]1([CH2:4][NH:5][C@:6]23[CH2:41][CH2:40][C@@H:39]([C:42]([CH3:44])=[CH2:43])[C@@H:7]2[C@@H:8]2[C@@:21]([CH3:24])([CH2:22][CH2:23]3)[C@@:20]3([CH3:25])[C@@H:11]([C@:12]4([CH3:38])[C@@H:17]([CH2:18][CH2:19]3)[C:16]([CH3:27])([CH3:26])[C:15]([C:28]3[CH:37]=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][CH:29]=3)=[CH:14][CH2:13]4)[CH2:10][CH2:9]2)[CH2:3][CH2:2]1.[OH-].[Na+]>O1CCOCC1>[CH:1]1([CH2:4][NH:5][C@:6]23[CH2:41][CH2:40][C@@H:39]([C:42]([CH3:44])=[CH2:43])[C@@H:7]2[C@@H:8]2[C@@:21]([CH3:24])([CH2:22][CH2:23]3)[C@@:20]3([CH3:25])[C@@H:11]([C@:12]4([CH3:38])[C@@H:17]([CH2:18][CH2:19]3)[C:16]([CH3:26])([CH3:27])[C:15]([C:28]3[CH:37]=[CH:36][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=3)=[CH:14][CH2:13]4)[CH2:10][CH2:9]2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68358124methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(cyclopropylmethylamino)-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

Product 1

HCID 683581044-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(cyclopropylmethylamino)-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 acidYield 27%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

To a cloudy mixture of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(cyclopropylmethylamino)-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 (0.024 g, 0.040 mmol) in 1,4-dioxane (1.5 mL) was added NaOH (1N) (0.5 mL, 0.5 mmol). The mixture was heated to 65° C. After two hours, the mixture was cooled to rt and stirred at rt overnight. The mixture was filtered through plug of glass wool and was purified by prep HPLC to afford the title compound (0.007 g, 10.79 μmol, 26.9% yield) as a white film. LCMS: m/e 584.6 (M+H)+, 1.83 min (method 2). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.00 (2H, d, J=8.0 Hz), 7.21 (2H, d, J=8.0 Hz), 5.31 (1H, d, J=5.0 Hz), 4.75 (1H, d, J=1.5 Hz), 4.61 (1H, s), 2.76 (1H, td, J=10.9, 5.6 Hz), 2.62 (1H, dd, J=11.2, 6.1 Hz), 2.23 (1H, dd, J=11.5, 7.8 Hz), 1.97-2.16 (3H, m), 1.82-1.95 (2H, m), 1.70 (3H, s), 1.16 (3H, s), 1.01 (3H, s), 1.00 (3H, s), 0.96 (3H, s), 0.95 (3H, s), 0.80-1.77 (19H, m), 0.48-0.58 (2H, m), 0.09-0.24 (2H, m).

Workup

  1. temperaturethe mixture was cooled to rt
  2. filtrationThe mixture was filtered through plug of glass wool
  3. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-41aad92ef52c47eca8bcf6728274f568
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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