Ethanol → 2-Acetylfuro-1,4-naphthoquinone

HRID 1525608Notes

Reaction equation

HRID 1525608 reaction equation
[OH:1][C:2]1[C:3](=[O:13])[C:4]2[C:9]([C:10](=[O:12])[CH:11]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.N12CCCN=C1C[CH2:18][CH2:17][CH2:16][CH2:15]2.C([OH:27])C>>[C:16]([C:17]1[O:1][C:2]2[C:3](=[O:13])[C:4]3[C:9]([C:10](=[O:12])[C:11]=2[CH:18]=1)=[CH:8][CH:7]=[CH:6][CH:5]=3)(=[O:27])[CH3:15]

Participants

4

Reactant 3

HCID 702EthanolHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 178516607HCID 178516607, compound

Product 1

HCID 103318442-Acetylfuro-1,4-naphthoquinone

Procedure

The synthetic process for preparing Crystal Form 3 is shown in FIGS. 6A-6D. The steps are outlined briefly herein. Step 1: 3-Butene-2-one (methyl vinyl ketone, MVK) is brominated using bromine. No additional solvent is used. The intermediate 3,4-dibromobutan-2-one is dissolved in tetrahydrofuran (THF) and reacted with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to form a second intermediate, 3-bromo-3-buten-2-one. Once this reaction is complete, 2-hydroxy-1,4-naphthoquinone (HNQ) is added. A second portion of DBU is added, and the mixture is exposed to air. The reaction is quenched with water and the solids are collected by filtration. These solids are washed with aqueous sodium bicarbonate, aqueous acetic acid, water, and ethanol. The product is isolated by slurrying in ethanol and collecting the solids. Step 2: Residual amounts of the 2-acetyl-2,3-dihydronaphtho[2,3-b]furan-4,9-dione that accompany the desired 2-acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione (Compound 1) are oxidized to Compound 1 with activated manganese dioxide in toluene. The mixture is filtered through a cake of charcoal and Celite. The filtrate is concentrated to precipitate the product, which is filtered and dried. Step 3: The solids are slurried in ethyl acetate (25 mL/g purified Compound 1) at 75° C.-80° C. for about 5 hr, collected by filtration, and dried. Compound 1 produced with this method is Crystal Form 3. Compound 1 produced with this method without the slurry process yielded Crystal Form 1.

Workup

  1. customThe reaction is quenched with water
  2. filtrationthe solids are collected by filtration
  3. washThese solids are washed with aqueous sodium bicarbonate, aqueous acetic acid, water, and ethanol
  4. customThe product is isolated
  5. customcollecting the solids
  6. filtrationThe mixture is filtered through a cake of charcoal and Celite
  7. concentrationThe filtrate is concentrated
  8. customto precipitate the product, which
  9. filtrationis filtered
  10. customdried
  11. filtrationcollected by filtration
  12. customdried

Sources & evidence

ORD record
ord-576eb58309254861b2ae78d823a915a2
Source dataset
uspto-grants-2015_07
Patent number
US09084766B2

Reaction notes

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