2-Methyl-2-butene → (+)-Betulonic acid

HRID 338631Notes

Reaction equation

HRID 338631 reaction equation
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:24])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14](=[O:23])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:25]([C:28]([CH3:30])=[CH2:29])[CH2:26][CH2:27][C@:5]1([CH:31]=[O:32])[CH2:4][CH2:3]2.CC(=CC)C.Cl([O-])=[O:39].[Na+].O.OP([O-])(O)=O.[Na+]>CC(O)(C)C.O.[Cl-].[NH4+]>[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:24])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:21])([CH3:22])[C:14](=[O:23])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:25]([C:28]([CH3:30])=[CH2:29])[CH2:26][CH2:27][C@:5]1([C:31]([OH:39])=[O:32])[CH2:4][CH2:3]2

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 473111BetulonalHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium Chlorite

Product 1

HCID 122844(+)-Betulonic acidYield 100%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-9-oxo-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carbaldehyde (17.6 g, 36.1 mmol) in t-BuOH (100 mL) was added 2-methyl-2-butene (40 mL, 476 mmol). A solution of sodium chlorite (15 g, 133 mmol) and sodium phosphate monobasic monohydrate (25 g, 181 mmol) in water (200 mL) was added drop wise over 1.25 h and the mixture was stirred at rt for an additional 45 minutes. The mixture was diluted with saturated aqueous ammonium chloride (100 mL) and extracted with ethyl acetate (3×125 mL). The combined organic layers were washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by using a 300 g Thomson silica gel column and a 10-50% ethyl acetate in hexanes gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to give (1R,3aS,5aR,5bR,7aR,11aR,11bR,13 aR,13bR)-5a,5b,8,8,11a-pentamethyl-9-oxo-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid as a white foam (16.4 g, 36.1 mmol, 100%). LCMS: m/e 453.2 (M−H)−, 2.61 min (method 3). 1H NMR (400 MHz, chloroform-d) δ=10.02 (br. s., 1H), 4.75 (d, J=1.8 Hz, 1H), 4.64-4.61 (m, 1H), 3.02 (td, J=10.8, 4.8 Hz, 1H), 2.55-2.36 (m, 3H), 2.33-2.19 (m, 2H), 2.08-1.86 (m, 4H), 1.70 (s, 3H), 1.08 (s, 3H), 1.02 (s, 3H), 1.00 (s, 3H), 0.98 (s, 3H), 0.93 (s, 3H), 1.82-0.90 (m, 15H).

Workup

  1. extractionextracted with ethyl acetate (3×125 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe drying agent was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9fdb58fd71ab4d9daa2343731028c309
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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