Sulfuric Acid → methyl 2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoate

HRID 966429Notes

Reaction equation

HRID 966429 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]([C:23]([OH:25])=[O:24])=[C:5]([C:7]2[C:17]3[CH:18]=[CH:19][C:20]([OH:22])=[CH:21][C:16]=3[O:15][C:14]3[C:8]=2[CH:9]=[CH:10][C:11]([CH:13]=3)=[O:12])[CH:6]=1.S(=O)(=O)(O)O.[C:31](=O)(O)[O-].[Na+]>CO>[CH3:31][O:24][C:23]([C:4]1[C:5]([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([OH:12])=[CH:13][C:14]=3[O:15][C:16]3[C:17]=2[CH:18]=[CH:19][C:20]([CH:21]=3)=[O:22])=[CH:6][CH:1]=[CH:2][CH:3]=1)=[O:25]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 33832-(6-Hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 404882methyl 2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoateYield 88.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

Fluorescein (10 g; 30 mmol) was dispersed in methanol (30 mL) and concentrated sulfuric acid was added slowly. After the addition was complete the mixture was stirred with heating at 120° C. for 14 hours. After cooling the mixture, sodium bicarbonate was added to neutralize the mixture to give a solid. The crude product was filtered and washed with 2% sodium bicarbonate (200 mL), with water (4×) and with 1% acetic acid to give the fluorescein methyl ester (9.2 g, 26.4 mmol, 88.2% yield), m.p. 260-261° C. Step 8B. The fluorescein methyl ester (8 g, 23.1 mmol) and potassium carbonate (9.6 g, 69.3 mmol) were dissolved in dimethylformamide (50 mL) at 90° C. and to the solution was added toluenesulfonyl chloride (6.6 g, 34.7 mmol) slowly for 30 minutes. The mixture was then further stirred with heating at 110° C. for 5 hours. The mixture, after being cooled to room temperature, was poured into water (1L) to give a precipitate which was collected by filtration and washed with water to give the product(10 g, 20 mmol, 86.5% yield). Step 8c. The toluenesulfonyl fluorescein ester (2 g, 4 mmol) and indoline (1.4 g, 12 mmol) were dissolved in N-methylpyrollidinone (100 mL) and the solution was stirred with heating at 95° C. for 17 hours. After being cooled to room temperature the mixture was poured into water (600 mL) to form a precipitate. The precipitate was filtered, washed with water and dried to give the ester (1.7 g, 3.9 mmol, 96.8% yield). The desired dye was obtained by basic hydrolysis of the ester using the following method: the dye and aqueous sodium hydroxide (3 eq.) were dissolved in methanol and stirred with heating at 60° C. for 1 hour until TLC showed complete conversion. The crude product was purified by column chromatography (5% methanol in methylene chloride) to give the desired product. (1.35 g, 3.1 mmol, 78% yield) The structure was confirmed by NMR and mass spectroscopy.

Workup

  1. additionAfter the addition
  2. additionwas added
  3. customto give a solid
  4. filtrationThe crude product was filtered
  5. washwashed with 2% sodium bicarbonate (200 mL), with water (4×) and with 1% acetic acid

Sources & evidence

ORD record
ord-a6cd3acc874145a2a0d0bfeba030a71a
Source dataset
uspto-grants-2005_10
Patent number
US06951952B2

Reaction notes

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