(4-Nitrophenyl)acetic acid → 4-Hydroxy-3-(4-nitrophenylacetyl)-coumarin

HRID 1870954Notes

Reaction equation

HRID 1870954 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].C1(N=C=NC2CCCCC2)CCCCC1.[OH:29][C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[O:33][C:32](=[O:40])[CH:31]=1>CN(C)C1C=CN=CC=1.ClCCCl>[OH:29][C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[O:33][C:32](=[O:40])[C:31]=1[C:11](=[O:13])[CH2:10][C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 4661(4-Nitrophenyl)acetic acidHCID 10868DicyclohexylcarbodiimideHCID 546829304-Hydroxycoumarin

Product 1

HCID 547123834-Hydroxy-3-(4-nitrophenylacetyl)-coumarinYield 19.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 111,2-DichloroethaneSolvent

Procedure

4-Nitrophenylacetic acid (4.5 g, 25 mmol) and then dicyclohexylcarbodiimide (5.4 g, 26 mmol) were added to a 1,2-dichloroethane (160 ml) suspension of 4-hydroxycoumarin (4.00 g, 24.6 mmol) at room temperature, after which 4-dimethylaminopyridine (0.15 g, 1.2 mmol) was added and stirring carried out for 1 hour at 60° C. and then further 4-dimethylaminopyridine (0.30 g, 2.4 mmol) added and stirring carried out for 23 hours at 85° C. The dicyclohexylurea was filtered off while the solution was still warm, then the reaction solution washed with dilute hydrochloric acid (50 ml), after which the aqueous layer was extracted with dichloromethane. After drying with anhydrous sodium sulphate, the solvent was distilled off and separation and purification performed by column chromatography. When recrystallization was performed from ethyl acetate, 4-hydroxy-3-(4-nitrophenylacetyl)-coumarin (1.56 g, 19%) was obtained as yellow crystals. Tetrahydrofuran (50 ml), methanol (18 ml) and concentrated hydrochloric acid (5 ml) were added to the compound (1.00 g, 3.1 mmol) obtained, then Pd-C (5%, containing 100% of water, 150 mg) added and the atmosphere replaced by hydrogen. The raw material was consumed in 4 hours and then the hydrogen replaced by argon.

Workup

  1. stirringstirring
  2. waitcarried out for 23 hours at 85° C
  3. filtrationThe dicyclohexylurea was filtered off while the solution
  4. temperaturewas still warm
  5. washthe reaction solution washed with dilute hydrochloric acid (50 ml)
  6. extractionafter which the aqueous layer was extracted with dichloromethane
  7. dry with materialAfter drying with anhydrous sodium sulphate
  8. distillationthe solvent was distilled off
  9. customseparation and purification
  10. customWhen recrystallization

Sources & evidence

ORD record
ord-de10959a277540a0afaf1fc4b10351a3
Source dataset
uspto-grants-2000_08
Patent number
US06100292

Reaction notes

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