Citric Acid → HCID 22467651, compound

HRID 1874759Notes

Reaction equation

HRID 1874759 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[Cl:10].C1C(=O)N(Br)C(=O)C1.[C:19]1(=[O:29])[NH:23][C:22](=[O:24])[C:21]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:20]12.[K].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)(Cl)(Cl)Cl.CC(N=NC(C#N)(C)C)(C#N)C>[Cl:10][C:4]1[CH:5]=[CH:6][C:7]([CH2:9][N:23]2[C:19](=[O:29])[C:20]3[C:21](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:22]2=[O:24])=[CH:8][C:3]=1[O:2][CH3:1]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 67184N-bromobutanimideHCID 993521-Chloro-2-methoxy-4-methylbenzeneHCID 24194345Phthalimide potassium salt

Product 1

HCID 22467651HCID 22467651, compoundYield 65.4%

Reagents, catalysts & solvents 2

HCID 6547AzobisisobutyronitrileCatalystHCID 5943Carbon TetrachlorideSolvent

Procedure

To a solution of 2-chloro-5-methylphenyl methyl ether (12.0 g, 76 mmol) dissolved in CCl4 (200 mL) was added NBS (215.0 g, 83.6 mmol) and AIBN (0.63 g, 3.8 mmol). The reaction mixture was placed in an oil bath at 85° C. and stirred for 2-4 h. The reaction was cooled to RT, filtered and the solid washed with CCl4. The filtrate was evaporated and the resulting solid was dissolved in DMF (200 mL) then potassium phthalimide (35.0 g, 192 mmol) was added. The reaction mixture was placed in an oil bath at 60° C. and stirred for 2 h. The reaction mixture was cooled to RT then 10% citric acid (200 mL) was added and the mixture was extracted with EtOAc (3×200 mL). The organic extracts were combined, washed with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered and evaporated. Purification was accomplished by column chromatography (hexane/EtOAc) to afford the title compound (15.0 g, 65%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 7.78-7.88 (m, 4H), 7.30 (d, 1H), 7.09 (d, 1H), 6.81 (dd, 1H), 4.72 (s, 2H), 3.80 (s, 3H). MS: m/z 324.0 (M+23).

Workup

  1. customThe reaction mixture was placed in an oil bath at 85° C.
  2. filtrationfiltered
  3. washthe solid washed with CCl4
  4. customThe filtrate was evaporated
  5. dissolutionthe resulting solid was dissolved in DMF (200 mL)
  6. customThe reaction mixture was placed in an oil bath at 60° C.
  7. stirringstirred for 2 h
  8. temperatureThe reaction mixture was cooled to RT
  9. extractionthe mixture was extracted with EtOAc (3×200 mL)
  10. washwashed with water (50 mL) and brine (50 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customevaporated
  14. customPurification

Sources & evidence

ORD record
ord-03b745881b424a16a3e0b2586901b03c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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