Ethyl formate → 7-(3-Carboxypropyl)-9-formyl-9H-fluorene-4-carboxylic acid

HRID 2088271Notes

Reaction equation

HRID 2088271 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][C:7]1[CH:19]=[C:18]2[C:10]([C:11]3[C:12]([C:20]([OH:22])=[O:21])=[CH:13][CH:14]=[CH:15][C:16]=3[CH2:17]2)=[CH:9][CH:8]=1)([OH:3])=[O:2].[CH:23](OCC)=[O:24].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[CH:23]([CH:17]1[C:16]2[CH:15]=[CH:14][CH:13]=[C:12]([C:20]([OH:22])=[O:21])[C:11]=2[C:10]2[C:18]1=[CH:19][C:7]([CH2:6][CH2:5][CH2:4][C:1]([OH:3])=[O:2])=[CH:8][CH:9]=2)=[O:24]

Participants

6

Reactant 4

HCID 8025Ethyl formate2×HCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 587760277-(3-Carboxypropyl)-9H-fluorene-4-carboxylic acid

Product 1

HCID 587760137-(3-Carboxypropyl)-9-formyl-9H-fluorene-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

In a dry argon-purged flask with a reflux condenser, 7-(3-carboxy-propyl)-4-fluorenecarboxylic acid (4.0 g, 0.0135 mol) was dissolved in anh. DMF (120 mL) at 40° C. Ethyl formate (40 mL, stored over K2CO3 anh.) was added followed by addition of potassium tert-butoxide 95% (12.8 g, 0.108 mol, added in 2 portions). The reaction was stirred at about 40° C.-50° C. for four hours with the addition of anh. DMF (80 mL), anhydrous THF (5 mL) and ethyl formate (25 mL) at various intervals to aid solubility. The reaction was then stirred another 17 hours at room temperature. The ethyl formate was evaporated at reduced pressure. The reaction was quenched with water (150 mL) and acidified to pH 2 with concentrated HCl. The product was twice extracted with ethyl acetate (600 mL then 200 mL). The combined organic layers were washed 3 times with brine, dried over sodium sulfate, filtered and evaporated to dryness. The crude product (4.7 g, ˜100%, purity 80%) contained some unreacted starting material. 1H-NMR (d6-DMSO): δ (ppm) 11.4 (s, 1H, formyl); 8.3-7.0 (m, 7H, Ar); 2.7 (m, 2H, CH2); 2.3 (m, 2H, CH2); 1.9 (m, 2H, CH2).

Workup

  1. customIn a dry argon-purged flask with a reflux condenser
  2. customThe ethyl formate was evaporated at reduced pressure
  3. customThe reaction was quenched with water (150 mL)
  4. extractionThe product was twice extracted with ethyl acetate (600 mL
  5. washThe combined organic layers were washed 3 times with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-b5691f70a5b64f23af9d1acab9e76613
Source dataset
uspto-grants-2013_05
Patent number
US08435505B2

Reaction notes

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