N-methyl-2-pyrrolidone → (9R)-4-Chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diol

HRID 579385Notes

Reaction equation

HRID 579385 reaction equation
[Cl:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C@:7]([OH:19])([C:15]([F:18])([F:17])[F:16])[C:6]=2[CH:5]=[C:4]([O:20]CCCC(O)=O)[CH:3]=1.CN1CCCC1=O.Cl.N1C=CC=CC=1>C(OCC)(=O)C>[Cl:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C@@:7]([C:15]([F:17])([F:18])[F:16])([OH:19])[C:6]=2[CH:5]=[C:4]([OH:20])[CH:3]=1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 10176127Pyridinium chlorideHCID 1175993164-[(9R)-4-Chloro-9-hydroxy-9-(trifluoromethyl)-9H-fluoren-2-yloxy]butyric acid

Product 1

HCID 117599289(9R)-4-Chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diolYield 57.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
200 °C

Procedure

To 4-[(9R)-4-chloro-9-hydroxy-9-(trifluoromethyl)-9H-fluoren-2-yloxy]butyric acid (50 g) were added N-methylpyrrolidone (200 ml) and pyridine hydrochloride (298 g), and the mixture was stirred at an oil bath temperature of 200° C. for 2 days. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (500 ml), and washed twice with water. The obtained aqueous layer was extracted again with ethyl acetate (300 ml). The combined organic layer was washed successively with water, 1N hydrochloric acid and saturated brine. To the obtained organic layer were added anhydrous magnesium sulfate and activated carbon (10 g), and the mixture was stirred at room temperature. The insoluble material was filtered off through celite. The solvent in the obtained organic layer was evaporated, hexane was added to the residue, and the mixture was stirred at room temperature. The precipitated solid was collected by filtration, and dried under reduced pressure at room temperature. The obtained crude product was dissolved in ethyl acetate (500 ml), washed 3 times with water, dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solvent in the filtrate was evaporated. To the residue was added hexane, and the mixture was stirred at room temperature. The precipitated solid was collected by filtration, dried under reduced pressure at room temperature to give the title compound (22.4 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed twice with water
  3. extractionThe obtained aqueous layer was extracted again with ethyl acetate (300 ml)
  4. washThe combined organic layer was washed successively with water, 1N hydrochloric acid and saturated brine
  5. additionTo the obtained organic layer were added anhydrous magnesium sulfate and activated carbon (10 g)
  6. stirringthe mixture was stirred at room temperature
  7. filtrationThe insoluble material was filtered off through celite
  8. customThe solvent in the obtained organic layer was evaporated
  9. additionhexane was added to the residue
  10. stirringthe mixture was stirred at room temperature
  11. filtrationThe precipitated solid was collected by filtration
  12. customdried under reduced pressure at room temperature
  13. customThe obtained crude product
  14. washwashed 3 times with water
  15. dry with materialdried over anhydrous magnesium sulfate
  16. filtrationThe insoluble material was filtered off
  17. customthe solvent in the filtrate was evaporated
  18. additionTo the residue was added hexane
  19. stirringthe mixture was stirred at room temperature
  20. filtrationThe precipitated solid was collected by filtration
  21. customdried under reduced pressure at room temperature

Sources & evidence

ORD record
ord-5e217f502a854028af7c3cfc57e5398c
Source dataset
uspto-grants-2015_05
Patent number
US09040717B2

Reaction notes

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