Lithium hydroxide, monohydrate → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((1R,3S)-3-(((benzyloxy)carbonyl)amino)-2,2-dimethylcyclobutanecarboxamido)-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 85610Notes

Reaction equation

HRID 85610 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:15][C@@H:14]([C:16]([NH:18][C@:19]23[CH2:54][CH2:53][C@@H:52]([C:55]([CH3:57])=[CH2:56])[C@@H:20]2[C@@H:21]2[C@@:34]([CH3:37])([CH2:35][CH2:36]3)[C@@:33]3([CH3:38])[C@@H:24]([C@:25]4([CH3:51])[C@@H:30]([CH2:31][CH2:32]3)[C:29]([CH3:40])([CH3:39])[C:28]([C:41]3[CH:50]=[CH:49][C:44]([C:45]([O:47]C)=[O:46])=[CH:43][CH:42]=3)=[CH:27][CH2:26]4)[CH2:23][CH2:22]2)=[O:17])[C:13]1([CH3:59])[CH3:58])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+]>C1COCC1.CO.O>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:15][C@@H:14]([C:16]([NH:18][C@:19]23[CH2:54][CH2:53][C@@H:52]([C:55]([CH3:57])=[CH2:56])[C@@H:20]2[C@@H:21]2[C@@:34]([CH3:37])([CH2:35][CH2:36]3)[C@@:33]3([CH3:38])[C@@H:24]([C@:25]4([CH3:51])[C@@H:30]([CH2:31][CH2:32]3)[C:29]([CH3:40])([CH3:39])[C:28]([C:41]3[CH:50]=[CH:49][C:44]([C:45]([OH:47])=[O:46])=[CH:43][CH:42]=3)=[CH:27][CH2:26]4)[CH2:23][CH2:22]2)=[O:17])[C:13]1([CH3:59])[CH3:58])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 89400571HCID 89400571, compound

Product 1

HCID 683582334-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((1R,3S)-3-(((benzyloxy)carbonyl)amino)-2,2-dimethylcyclobutanecarboxamido)-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 21.09%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((1R,3S)-3-(((benzyloxy)carbonyl)amino)-2,2-dimethylcyclobutanecarboxamido)-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 (135 mg, 0.168 mmol) in THF (5 mL), MeOH (2 mL) was added a solution of lithium hydroxide monohydrate (0.014 mL, 0.504 mmol) in water (1 mL). The reaction mixture was stirred at 75° C. After 4 h, the mixture was concentrated to a white paste. The crude material was dissolved in THF (1.75 mL), MeOH (1 mL) and 1N HCl (0.25 mL) and injected into a reverse phase prep-HPLC using HPLC method 11 and dried in a vacuum oven to give the title compound (30.4 mg, 0.035 mmol, 21.09% yield) as white solid. LCMS: m/e 789.4 (M+H)+, 3.14 min (method 8). 1H NMR (400 MHz, CHLOROFORM-d) δ 8.02 (d, J=8.3 Hz, 2H), 7.41-7.37 (m, 4H), 7.36 (d, J=3.4 Hz, 1H), 7.25 (d, J=8.3 Hz, 2H), 5.33 (d, J=4.6 Hz, 1H), 5.19-5.07 (m, 3H), 4.99 (br. s., 1H), 4.77 (s, 1H), 4.66 (s, 1H), 3.98-3.88 (m, 1H), 2.70-2.55 (m, 3H), 2.47-2.28 (m, 3H), 2.19-2.09 (m, 2H), 1.99-1.87 (m, 1H), 1.76 (d, J=7.8 Hz, 1H), 1.72 (s, 3H), 1.71-1.63 (m, 2H), 1.58 (d, J=8.1 Hz, 3H), 1.50 (br. s., 3H), 1.43 (br. s., 1H), 1.37 (br. s., 3H), 1.33 (d, J=12.2 Hz, 2H), 1.28 (s, 3H), 1.24 (d, J=7.1 Hz, 1H), 1.16 (d, J=12.2 Hz, 2H), 1.09 (s, 3H), 1.02 (s, 6H), 1.01 (br. s., 3H), 0.96 (s, 6H).

Workup

  1. concentrationthe mixture was concentrated to a white paste
  2. dissolutionThe crude material was dissolved in THF (1.75 mL)
  3. customdried in a vacuum oven

Sources & evidence

ORD record
ord-cef3885984484a6eb31493b7fe90577e
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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