Diazomethane → Artemisinic alcohol

HRID 1349931Notes

Reaction equation

HRID 1349931 reaction equation
[CH3:1][C@H:2]1[C@@H:7]2[CH2:8][CH2:9][C:10]([CH3:12])=[CH:11][C@@H:6]2[C@H:5]([C:13]([C:15](O)=[O:16])=[CH2:14])[CH2:4][CH2:3]1.[N+](=C)=[N-]>CCOCC>[CH3:1][C@H:2]1[C@@H:7]2[CH2:8][CH2:9][C:10]([CH3:12])=[CH:11][C@@H:6]2[C@H:5]([C:13]([CH2:15][OH:16])=[CH2:14])[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 9550DiazomethaneHCID 10922465Artemisinic Acid

Product 1

HCID 15983960Artemisinic alcohol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-60 °C

Procedure

Amorpha-4,11-diene-12-ol was prepared from 100 mg artemisinic acid. The acid was dissolved in 6 mL of dry ether and esterified by adding diazomethane and mixing for 1 hour. GC-MS analyses of the reaction mixture showed the methyl ester and another compound (3:1), probably the methyl ester that was not connected to a cyclopropyl group. After removal of ether, 8.6 mg of the mixture was dissolved in 20 mL of ether-TBF (1:1) and cooled at −60° C. under a flow of dry nitrogen for 2 hours. The mixture was subsequently stirred for 1 hour at −30° C. with an excess of LiAlH4, after which the reaction was stopped by the addition of Na2SO4.10H2O. The temperature was raised to room temperature, and the reaction mixture was stirred an additional half hour. After drying with MgSO4 overnight, the mixture was filtered through a Büichner funnel and the solvent removed. The desired alcohol was isolated and purified by preparative thin layer chromatography performed on silica gel plates, using a mixture of petroleum ether-ethyl acetate (3:1) as an eluent (Rf 0.7). Amorpha-4,11-diene-12-ol was obtained in an overall yield of 14% as a mixture with 4-amorphene-12-ol (9:1). 1H NMR (400 MHz, CDCl3): δ 0.87 (d, 3H, Me15, J=6.0 Hz), δ 1.50 (br s, 3H, Me14), δ 1.0–2.2 (m, 11H), δ 2.47 (m, 1H, H6), δ 4.10 (s, 2H, H12), δ 4.83 (br s, 1H, H13′), δ 5.04 (br s, 1H, H13), δ 5.18 (br s, 1H, H4). EIMS (70 eV) m/z: 220 [M]+ (6), 202 (35), 189 (66), 187 (34), 145 (40), 132 (52), 131 (36), 121 (100), 119 (81), 105 (51), 93 (74), 91 (70), 81 (47), 79 (77), 77 (50), 55 (41), 41 (47).

Workup

  1. additionmixing for 1 hour
  2. customAfter removal of ether, 8.6 mg of the mixture
  3. dissolutionwas dissolved in 20 mL of ether-TBF (1:1)
  4. additionafter which the reaction was stopped by the addition of Na2SO4.10H2O
  5. temperatureThe temperature was raised to room temperature
  6. stirringthe reaction mixture was stirred an additional half hour
  7. dry with materialAfter drying with MgSO4 overnight
  8. filtrationthe mixture was filtered through a Büichner funnel
  9. customthe solvent removed

Sources & evidence

ORD record
ord-c3677888ad4c430eb958c63ab761a962
Source dataset
uspto-grants-2007_05
Patent number
US07214507B2

Reaction notes

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