Sodium Bicarbonate → 2-Fluoro-9-oxo-9,10-dihydroacridine-3-carboxylic acid

HRID 970329Notes

Reaction equation

HRID 970329 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([C:11]([OH:13])=O)[C:8]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C(=O)(O)[O-].[Na+]>>[F:1][C:2]1[C:3]([C:4]([OH:6])=[O:5])=[CH:7][C:8]2[NH:14][C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:11](=[O:13])[C:9]=2[CH:10]=1

Participants

3

Reactant 2

HCID 516892Sodium Bicarbonate2×HCID 167483932-Fluoro-5-phenylamino-terephthalic Acid

Product 1

HCID 167481472-Fluoro-9-oxo-9,10-dihydroacridine-3-carboxylic acidYield 84%

Conditions

Temperature
165 °C

Procedure

To a round bottom flask containing polyphosphoric acid (254 g) at 165-172° C. was added finely ground compound 174D (15.0 g, 55.6 mmol) over 30 min. After the addition was complete, the reaction mixture was stirred for 10 min at 165° C. HPLC indicated that the reaction was complete. While at 165° C., the mixture was slowly added to a mixture of ice and sodium bicarbonate. The pH was adjusted to 3.0 with additional solid sodium bicarbonate, and the resulting mixture was filtered through a medium porosity fritted funnel to give a greenish-yellow paste which was washed with water (3×) and air-dried under vacuum. The resulting paste was rinsed with MeOH into a flask. The paste/MeOH mixture was then sonicated to disperse the paste. DCM was added, and the mixture was concentrated under reduced pressure. The azeotrope procedure was repeated 2× to give 12.0 g (84%) of acridone acid 174E as a yellow solid. HPLC retention time=2.35 min. (Condition A) and LC/MS M+1=258.03. 1H-NMR (500 MHz, DMSO) δ 7.30 (t, 1H, J=7.6 Hz), 7.56 (d, 1H, J=7.6 Hz), 7.78 (t, 1H, J=7.6 Hz), 7.93 (d, 1H, J=11.0 Hz), 8.11 (d, 1H, J=6.1 Hz), 8.22 (d, 1H, J=7.6 Hz), and 12.06 (s, 1H).

Workup

  1. additionAfter the addition
  2. filtrationthe resulting mixture was filtered through a medium porosity fritted funnel
  3. customto give a greenish-yellow paste which
  4. washwas washed with water (3×)
  5. customair-dried under vacuum
  6. washThe resulting paste was rinsed with MeOH into a flask
  7. customThe paste/MeOH mixture was then sonicated
  8. additionto disperse the paste
  9. additionDCM was added
  10. concentrationthe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-3b29ec031e1140aca154c7ea3cd4b384
Source dataset
uspto-grants-2007_12
Patent number
US07312209B2

Reaction notes

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