Water → 5-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(hydroxymethyl)-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]isoxazole-3-carboxylic acid

HRID 406889Notes

Reaction equation

HRID 406889 reaction equation
C([O:9][CH2:10][C@:11]12[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:43])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]2[O:37][N:36]=[C:35]([C:38]([O:40]CC)=[O:39])[CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1)(=O)C1C=CC=CC=1.O.O.[OH-].[Li+]>O1CCOCC1.Cl>[OH:9][CH2:10][C@:11]12[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:43])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:31])([CH3:32])[C:20]([C:33]2[O:37][N:36]=[C:35]([C:38]([OH:40])=[O:39])[CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 67777149Ethyl 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(benzoyloxymethyl)-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)isoxazole-3-carboxylate

Product 1

HCID 547608845-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(hydroxymethyl)-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]isoxazole-3-carboxylic acidYield 32,590.9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of ethyl 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(benzoyloxymethyl)-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)isoxazole-3-carboxylate (0.015 g, 0.022 mmol) in 1,4-Dioxane (2 mL) was added Water (0.5 mL) and Lithium hydroxide monohydrate (0.17 g, 4.05 mmol). The mixture was heated to 75° C. After 3.5 h the mixture was cooled to rt and was diluted with 1N HCl (7 mL) then was extracted with dichloromethane (4×7 mL). The combined organic layers were dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by crystallization using dioxane, water, and methanol. The expected product, 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(hydroxymethyl)-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)isoxazole-3-carboxylic acid (4 mg, 7.17 mmol, 31.9% yield), was isolated as a white solid. LCMS: m/e 536.35 (M+H)+, 2.03 min (method 7). 1H NMR (500 MHz, Pyr) δ ppm 0.87 (s, 3H), 0.96-1.88 (m, 20H), 1.04 (s, 3H), 1.05 (s, 3H), 1.17 (s, 3H), 1.21 (s, 3H), 1.81 (s, 3H), 2.14-2.27 (m, 1H), 2.39-2.53 (m, 1H), 2.59-2.74 (m, 1H), 3.70 (d, J=10.99 Hz, 1H), 4.12 (d, J=10.99 Hz, 1H), 4.80 (br. s., 1H), 4.94 (s, 1H), 6.40 (d, J=6.41 Hz, 1H), 7.08 (s, 1H).

Workup

  1. temperatureAfter 3.5 h the mixture was cooled to rt
  2. extractionthen was extracted with dichloromethane (4×7 mL)
  3. dry with materialThe combined organic layers were dried with Na2SO4
  4. customThe drying agent was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by crystallization

Sources & evidence

ORD record
ord-287a6ae7e9884b1a9255a42709c1da5d
Source dataset
uspto-grants-2014_06
Patent number
US08754068B2

Reaction notes

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