Hydrochloric Acid → HCID 59192517, compound

HRID 2384011Notes

Reaction equation

HRID 2384011 reaction equation
[F:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:9].[C:10]1(=[O:16])[O:15][C:13](=[O:14])[CH2:12][CH2:11]1.[Cl-].[Al+3].[Cl-].[Cl-].Cl>ClC(Cl)C(Cl)Cl>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([C:10](=[O:16])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[C:3]([OH:9])[C:2]=1[F:1]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7922Succinic anhydrideHCID 27737123-Chloro-2-fluorophenolHCID 6451240Aluminum(III) Chloride

Product 1

HCID 59192517HCID 59192517, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 65911,1,2,2-TetrachloroethaneSolvent

Conditions

Temperature
130 °C

Procedure

To a stirred and cooled solution of 2-fluoro-3-chloro-phenol (21.9 g, 0.15 mol) and succinic anhydride (15.3 g, 0.15 mol) in 1,1,2,2-tetrachloroethane (135 mL) was added anhydrous aluminum chloride (38.7 g, 0.29 mol) portion-wise. The reaction mixture was stirred at room temperature for 3 hours and then heated at 130° C. for 2 hours. After being cooled to room temperature, to the reaction mixture were added concentrated hydrochloric acid and ice alternatively in small portions. The resulting mixture was extracted with ethyl acetate (75 mL×3). The combined organic layers were evaporated. The solid residue was basified by slow addition of an aqueous solution of 2N sodium hydroxide solution under cooling conditions, and then extracted with ethyl acetate (30 mL×3). The aqueous layer was acidified by dropwise addition of concentrated hydrochloric acid to a pH of about 2, and then extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Column chromatography (silica gel, 100-120 mesh, 15% ethyl acetate in hexane) gave 4-(4-chloro-3-fluoro-2-hydroxy-phenyl)-4-oxo-butyric acid (7.0 g, 19%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.59 (t, J=6.26 Hz, 2H), 3.31 (t, J=6.28 Hz, 2H), 7.15 (d, J=6.56 Hz, 1H), 7.74 (d, J=6.56 Hz, 1H), 11.90-12.31 (m, 2H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 hours
  2. temperatureAfter being cooled to room temperature, to the reaction mixture
  3. extractionThe resulting mixture was extracted with ethyl acetate (75 mL×3)
  4. customThe combined organic layers were evaporated
  5. additionThe solid residue was basified by slow addition of an aqueous solution of 2N sodium hydroxide solution under cooling conditions
  6. extractionextracted with ethyl acetate (30 mL×3)
  7. additionThe aqueous layer was acidified by dropwise addition of concentrated hydrochloric acid to a pH of about 2
  8. extractionextracted with ethyl acetate (50 mL×3)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d55a75bf9f084c9f9b375aaaee03b9a4
Source dataset
uspto-grants-2012_09
Patent number
US08263656B2

Reaction notes

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