Potassium Carbonate → Coumarin

HRID 900214Notes

Reaction equation

HRID 900214 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](O)=O)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.CC(C1C=CC(F)=CC=1O)=O.[C:35](=O)([O-:37])[O-:36].[K+].[K+]>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[O:37]1[C:6]2[CH:7]=[CH:2][CH:3]=[CH:4][C:5]=2[CH:8]=[CH:9][C:35]1=[O:36]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 15880(4-Chlorophenyl)acetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 27373264'-Fluoro-2'-hydroxyacetophenone

Product 1

HCID 323CoumarinYield 38%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-chlorophenylacetic acid (11.05 g, 64.8 mmol) in DMF (100 mL) was treated with CDI (13.13 g, 81 mmol) in several portions over about 15 minutes and the mixture was stirred until gas evolution had ceased. 4-Fluoro-2-hydroxyacetophenone (5.0 g, 32.4 mmol) was added followed by potassium carbonate (15.7 g, 113.6 mmol) and 4-DMAP (about 1 g). The reaction mixture was warmed at about 80° C. for about 10 h then cooled to room temperature. Water (200 mL) was added and the aqueous layer was extracted with ethyl acetate. The combined organic layer was concentrated and the crude product was purified by flash chromatography (ethyl acetate/hexanes) to give a yield of about 3.5 g (38%) of a benzopyranone intermediate.

Workup

  1. temperaturethen cooled to room temperature
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. concentrationThe combined organic layer was concentrated
  4. customthe crude product was purified by flash chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f226b455b4414ec39c91d1d158317971
Source dataset
uspto-grants-2008_04
Patent number
US07358274B2

Reaction notes

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