Lithium Hydroxide → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)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)benzoic acid

HRID 338648Notes

Reaction equation

HRID 338648 reaction equation
[C@H:1]12[CH2:49][C@H:4]([N:5]([CH2:7][CH2:8][NH:9][C@:10]34[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:11]3[C@@H:12]3[C@@:25]([CH3:28])([CH2:26][CH2:27]4)[C@@:24]4([CH3:29])[C@@H:15]([C@:16]5([CH3:42])[C@@H:21]([CH2:22][CH2:23]4)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]4[CH:41]=[CH:40][C:35]([C:36]([O:38]C)=[O:37])=[CH:34][CH:33]=4)=[CH:18][CH2:17]5)[CH2:14][CH2:13]3)[CH2:6]1)[CH2:3][O:2]2.[OH-].[Li+]>C1COCC1.CO>[C@H:1]12[CH2:49][C@H:4]([N:5]([CH2:7][CH2:8][NH:9][C@:10]34[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:11]3[C@@H:12]3[C@@:25]([CH3:28])([CH2:26][CH2:27]4)[C@@:24]4([CH3:29])[C@@H:15]([C@:16]5([CH3:42])[C@@H:21]([CH2:22][CH2:23]4)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]4[CH:33]=[CH:34][C:35]([C:36]([OH:38])=[O:37])=[CH:40][CH:41]=4)=[CH:18][CH2:17]5)[CH2:14][CH2:13]3)[CH2:6]1)[CH2:3][O:2]2

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86701810methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)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)benzoate

Product 1

HCID 722026434-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)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)benzoic acidYield 59.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)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)benzoate (99 mg, 0.148 mmol) in THF (2 mL) and MeOH (0.5 mL) was added 3N lithium hydroxide (0.197 mL, 0.592 mmol). The reaction mixture was stirred at 75° C. After 3.5 h, the reaction was cooled to rt and concentrated to a white paste which was purified by reverse phase prep-HPLC using prep method 6 and dried under vacuum to give the title compound (81.4 mg, 0.088 mmol, 59.2% yield) as a white solid. LC/MS: m/e 655.5 (M+H)+, 3.76 min (method 8). 1H NMR (400 MHz, 1:1 CHLOROFORM-d:METHANOL-d4) δ 7.90 (d, J=8.3 Hz, 2H), 7.18 (d, J=8.3 Hz, 2H), 5.35-5.23 (m, 1H), 4.79 (s, 1H), 4.70 (s, 1H), 4.58 (br. s., 1H), 4.08 (d, J=9.0 Hz, 1H), 4.02 (br. s., 1H), 3.76 (dd, J=9.3, 1.5 Hz, 1H), 3.30-3.21 (m, 2H), 3.16 (d, J=10.3 Hz, 2H), 3.00 (br. s., 1H), 2.74 (td, J=11.1, 5.5 Hz, 1H), 2.18-1.94 (m, 7H), 1.91-1.84 (m, 1H), 1.82-1.75 (m, 1H), 1.71 (s, 3H), 1.70-1.63 (m, 2H), 1.63-1.30 (m, 11H), 1.28-1.17 (m, 2H), 1.14 (s, 3H), 1.07 (s, 3H), 1.00 (s, 3H), 0.93 (s, 3H), 0.92 (br. s., 3H).

Workup

  1. temperaturethe reaction was cooled to rt
  2. concentrationconcentrated to a white paste which
  3. customwas purified by reverse phase prep-HPLC using prep method 6
  4. customdried under vacuum

Sources & evidence

ORD record
ord-4b34d342942d45d98d47a7c4caba3c4d
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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