Hydrochloric Acid → 4-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(isopentylcarbamoyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoic acid

HRID 2405519Notes

Reaction equation

HRID 2405519 reaction equation
[CH2:1]([NH:6][C:7]([C@:9]12[CH2:44][CH2:43][C@@H:42]([C:45]([CH3:47])=[CH2:46])[C@@H:10]1[C@@H:11]1[C@@:24]([CH3:27])([CH2:25][CH2:26]2)[C@@:23]2([CH3:28])[C@@H:14]([C@:15]3([CH3:41])[C@@H:20]([CH2:21][CH2:22]2)[C:19]([CH3:30])([CH3:29])[C:18]([C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37]C)=[O:36])=[CH:33][CH:32]=2)=[CH:17][CH2:16]3)[CH2:13][CH2:12]1)=[O:8])[CH2:2][CH:3]([CH3:5])[CH3:4].O.[OH-].[Li+].Cl>C1COCC1.O>[CH2:1]([NH:6][C:7]([C@:9]12[CH2:44][CH2:43][C@@H:42]([C:45]([CH3:47])=[CH2:46])[C@@H:10]1[C@@H:11]1[C@@:24]([CH3:27])([CH2:25][CH2:26]2)[C@@:23]2([CH3:28])[C@@H:14]([C@:15]3([CH3:41])[C@@H:20]([CH2:21][CH2:22]2)[C:19]([CH3:29])([CH3:30])[C:18]([C:31]2[CH:40]=[CH:39][C:34]([C:35]([OH:37])=[O:36])=[CH:33][CH:32]=2)=[CH:17][CH2:16]3)[CH2:13][CH2:12]1)=[O:8])[CH2:2][CH:3]([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67774457methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(isopentylcarbamoyl)-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 547648814-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(isopentylcarbamoyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoic acidYield 88.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(isopentylcarbamoyl)-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 (0.204 g, 0.318 mmol) in THF (5 mL) was added a solution of lithium hydroxide monohydrate (0.040 g, 0.953 mmol) in H2O (1.000 mL). The resulting white slurry was stirred at rt overnight. After 15 h, TLC showed significant starting material left thus reaction was heated to 75° C. for 3 h. Reaction was treated with 1N HCl (1 mL) and concentrated to dryness. Material was absorpted onto silica gel, loaded onto a silica gel column (12 g cartridge) and was eluted with 0% B to 100% B for 180 mL and held 100% B for 600 mL (Solvents: A=100% DCM, B=90:10 DCM:MeOH). Obtained 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(isopentylcarbamoyl)-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 (182 mg, 0.281 mmol, 88% yield) as white solid. LCMS: m/e 628.6 (M−H)+, 2.45 min (method 5); 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.0 (2H, d, J=8.2 Hz), 7.3 (2H, d, J=8.5 Hz), 5.6 (1H, t, J=5.6 Hz), 5.3 (1H, dd, J=6.1, 1.8 Hz), 4.8 (1H, d, J=2.1 Hz), 4.6-4.6 (1H, m), 3.3-3.4 (1H, m), 3.2-3.3 (2H, m), 2.5-2.6 (1H, m), 2.1 (1H, dd, J=17.4, 6.4 Hz), 1.9-2.1 (2H, m), 1.7-1.8 (2H, m), 1.7 (3H, s), 1.6-1.7 (3H, m), 1.3-1.6 (11H, m), 1.2-1.3 (2H, m), 1.0 (6H, s), 1.0 (3H, s), 1.0 (6H, s), 0.9-1.0 (6H, m) 13C NMR(CHLOROFORM-d) δ ppm 14.4, 15.6, 16.2, 19.3, 19.5, 20.8, 21.1, 22.2, 22.3, 25.5, 25.7, 29.2, 30.7, 33.4, 33.6, 36.0, 37.2, 37.7, 38.2, 38.5, 40.4, 41.5, 42.2, 46.5, 49.3, 49.9, 52.6, 55.4, 77.3, 109.0, 124.0, 126.7, 128.9, 129.9, 145.9, 149.4, 150.8, 171.1, 175.7.

Workup

  1. waitAfter 15 h
  2. waitleft thus
  3. customreaction
  4. temperaturewas heated to 75° C. for 3 h
  5. customReaction
  6. concentrationconcentrated to dryness
  7. washwas eluted with 0% B to 100% B for 180 mL

Sources & evidence

ORD record
ord-80183117f07243adaeabda778866665a
Source dataset
uspto-grants-2014_08
Patent number
US08802661B2

Reaction notes

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