Ethyl Acetate → (+)-Betulonic acid

HRID 1400997Notes

Reaction equation

HRID 1400997 reaction equation
[OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C@@H:4]([CH2:5][CH2:6][C@:7]3([CH3:31])[C@@H:16]2[CH2:15][CH2:14][C@H:13]2[C@@:8]3([CH3:30])[CH2:9][CH2:10][C@@:11]3([C:27]([OH:29])=[O:28])[CH2:23][CH2:22][C@@H:21]([C:24]([CH3:26])=[CH2:25])[C@@H:12]32)[C:3]1([CH3:33])[CH3:32].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.C(OCC)(=O)C>CN(C=O)C>[CH3:30][C@:8]12[C@@:7]3([CH3:31])[C@@H:16]([C@:17]4([CH3:20])[C@@H:4]([CH2:5][CH2:6]3)[C:3]([CH3:32])([CH3:33])[C:2](=[O:1])[CH2:19][CH2:18]4)[CH2:15][CH2:14][C@@H:13]1[C@H:12]1[C@H:21]([C:24]([CH3:26])=[CH2:25])[CH2:22][CH2:23][C@:11]1([C:27]([OH:29])=[O:28])[CH2:10][CH2:9]2

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 64971Betulinic AcidHCID 2724130Cornforth reagent3×

Product 1

HCID 122844(+)-Betulonic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a chilled solution of (1R,3 aS,5aR,5bR,7aR,9S,11aR,11bR,13 aR,13bR)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (2.35 g, 5.15 mmol) in DMF (45 mL) at ˜4° C. under nitrogen was added pyridinium dichromate (PDC 3.87 g, 10.29 mmol) in a single portion. The suspension was rapidly stirred, forming an orange solution, but rapidly changed into dark brownish with all the PDC dissolved into the reaction mixture. The reaction was kept in an ice bath, and was allowed to warm to RT slowly over 8 hours. Stirring continued for 48 hrs at RT thereafter. The PDC reaction mixture acquired a dull dark brownish appearance but no PPT was observed. The crude DMF reaction solution was poured into vigorously stirred ethyl acetate (400 mL) causing a PPT of a light brownish solid. The suspension was filtered through a short bed (˜1″ thick) of silica gel type-H in a large diameter filter funnel. The clear filtrate was washed with 0.1 N HCl (200 mL), then with water (3×200 mL). All the volatile solvents were removed, giving 2.1 gm (88%) as a white solid. MS: m/e 477.21 (M+Na)+, 6.2 min (method 9). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.76 (d, J=2.3 Hz, 1H), 4.63 (s, 1H), 3.06-2.98 (m, 1H), 2.55-2.37 (m, 2H), 2.28 (s, 2H), 1.99 (d, J=6.5 Hz, 2H), 1.95-1.87 (m, 1H), 1.71 (s, 3H), 1.64 (t, J=11.4 Hz, 2H), 1.59-1.20 (m, 16H), 1.08 (s, 3H), 1.03 (s, 3H), 1.00 (s, 3H), 0.99 (s, 3H), 0.94 (s, 3H).

Workup

  1. customforming an orange solution
  2. dissolutiondissolved into the reaction mixture
  3. customThe reaction was kept in an ice bath
  4. stirringStirring
  5. filtrationThe suspension was filtered through a short bed (˜1″ thick) of silica gel type-H in a large diameter
  6. filtrationfilter funnel
  7. washThe clear filtrate was washed with 0.1 N HCl (200 mL)
  8. customAll the volatile solvents were removed
  9. customgiving 2.1 gm (88%) as a white solid
  10. customm/e 477.21 (M+Na)+, 6.2 min (method 9)

Sources & evidence

ORD record
ord-07157ea08d334b12b2c9856c16285f57
Source dataset
uspto-grants-2014_12
Patent number
US08906889B2

Reaction notes

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