Reaction #1150

Reaction equation

methyl 2-formyl-5-methoxyphenoxyacetate

1,8-diazabicyclo[5.4.0]-7-undecene

→

methyl 6-methoxybenzofuran-2-carboxylate

Yield 57.0%

Solvents

toluene

Conditions

Workup

1. 1
   Temperaturewas heated under refluxing conditions for 4 hours
2. 2
   ConcentrationThe reaction mixture was concentrated under reduced pressure
3. 3
   workup.ADDITIONafter 6N hydrochloric acid was added
4. 4
   Extractionthe residue was extracted with ethyl acetate
5. 5
   WashAfter the ethyl acetate layer was washed with water
6. 6
   Dryingdried (MgSO4)
7. 7
   workup.DISTILLATIONthe solvent was distilled off
8. 8
   workup.ADDITION10% hydrochloric acid-methanol (30 ml) was added to the residue
9. 9
   Temperatureby heating at 70° to 80° C. for 4 hours
10. 10
    ConcentrationThe reaction mixture was concentrated under reduced pressure
11. 11
    workup.ADDITIONwater was added
12. 12
    Extractionfollowed by extraction with ethyl acetate
13. 13
    WashAfter the ethyl acetate layer was washed with water
14. 14
    Dryingdried (MgSO4)
15. 15
    workup.DISTILLATIONthe solvent was distilled off
16. 16
    WashFrom the fraction eluted with chloroform-hexane (1:2

Procedure

A mixture of methyl 2-formyl-5-methoxyphenoxyacetate (27.7 g), 1,8-diazabicyclo[5.4.0]-7-undecene (40.8 g) and toluene (200 ml) was heated under refluxing conditions for 4 hours. The reaction mixture was concentrated under reduced pressure; after 6N hydrochloric acid was added, the residue was extracted with ethyl acetate. After the ethyl acetate layer was washed with water and dried (MgSO4), the solvent was distilled off; 10% hydrochloric acid-methanol (30 ml) was added to the residue, followed by heating at 70° to 80° C. for 4 hours. The reaction mixture was concentrated under reduced pressure; water was added, followed by extraction with ethyl acetate. After the ethyl acetate layer was washed with water and dried (MgSO4), the solvent was distilled off; the residue was subjected to silica gel column chromatography. From the fraction eluted with chloroform-hexane (1:2, v/v), methyl 6-methoxybenzofuran-2-carboxylate (14.3 g, 57%) was obtained, which was then recrystallized from dichloromethane-isopropyl ether to yield colorless prisms having a melting point of 97° to 98° C.

Source