Betulin → Betulonal

HRID 338630Notes

Reaction equation

HRID 338630 reaction equation
[OH:1][CH2:2][C@:3]12[CH2:29][CH2:28][C@@H:27]([C:30]([CH3:32])=[CH2:31])[C@@H:4]1[C@@H:5]1[C@@:18]([CH3:21])([CH2:19][CH2:20]2)[C@@:17]2([CH3:22])[C@@H:8]([C@:9]3([CH3:26])[C@@H:14]([CH2:15][CH2:16]2)[C:13]([CH3:24])([CH3:23])[C@@H:12]([OH:25])[CH2:11][CH2:10]3)[CH2:7][CH2:6]1.C[N+]1([O-])CCOCC1>C(#N)C.C(Cl)Cl.CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O>[CH3:21][C@:18]12[C@@:17]3([CH3:22])[C@@H:8]([C@:9]4([CH3:26])[C@@H:14]([CH2:15][CH2:16]3)[C:13]([CH3:23])([CH3:24])[C:12](=[O:25])[CH2:11][CH2:10]4)[CH2:7][CH2:6][C@@H:5]1[C@H:4]1[C@H:27]([C:30]([CH3:32])=[CH2:31])[CH2:28][CH2:29][C@:3]1([CH:2]=[O:1])[CH2:20][CH2:19]2

Participants

6

Reactant 2

HCID 72326BetulinHCID 82029Methyl morpholine oxide2×

Product 1

HCID 473111Betulonal

Reagents, catalysts & solvents 3

HCID 178419074HCID 178419074, compoundCatalyst2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To suspension of (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (20 g, 45.2 mmol) in acetonitrile (200 mL) and DCM (300 mL) was added 4 angstrom molecular sieves (5 g) and the mixture was stirred for 10 minutes at rt. To the mixture was then added NMO (15.88 g, 136 mmol) and TPAP (0.794 g, 2.259 mmol). The dark green mixture was stirred under nitrogen overnight. Additional NMO (2.0 g) and TPAP (0.08 g) were added and the mixture was stirred at rt for 7 h. The mixture was filtered through a pad of silica gel and celite which was washed with dichloromethane then 25% EtOAc in hexanes. The filtrate was concentrated under reduced pressure and purified using a Thomson 240 g silica gel column and a 15-20% ethyl acetate in hexanes gradient. The title product was isolated as a white foam (17.6 g, 40.1 mmol, 89%). 1H NMR (400 MHz, chloroform-d) δ=9.68 (d, J=1.5 Hz, 1H), 4.77 (d, J=2.0 Hz, 1H), 4.66-4.63 (m, 1H), 2.89 (td, J=11.2, 5.8 Hz, 1H), 2.56-2.36 (m, 2H), 2.16-2.03 (m, 2H), 1.97-1.84 (m, 2H), 1.71 (s, 3H), 1.08 (s, 3H), 1.03 (s, 3H), 1.00 (s, 3H), 0.97 (s, 3H), 0.94 (s, 3H), 1.83-0.87 (m, 18H).

Workup

  1. additionwas added 4 angstrom molecular sieves (5 g)
  2. stirringThe dark green mixture was stirred under nitrogen overnight
  3. stirringthe mixture was stirred at rt for 7 h
  4. filtrationThe mixture was filtered through a pad of silica gel and celite which
  5. washwas washed with dichloromethane
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. custompurified

Sources & evidence

ORD record
ord-89e7238c13314154b2bdb2da4f559e27
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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