4-Nitrophenol → HCID 86672959, compound

HRID 1023281Notes

Reaction equation

HRID 1023281 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([C:12]([OH:14])=[O:13])[C:9]([OH:11])=[O:10].S(Cl)(Cl)=O.[N+:19]([C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=1)([O-:21])=[O:20]>C1(C)C=CC=CC=1.CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([C:9]([O:11][C:25]1[CH:26]=[CH:27][C:22]([N+:19]([O-:21])=[O:20])=[CH:23][CH:24]=1)=[O:10])[C:12]([O:14][C:25]1[CH:26]=[CH:27][C:22]([N+:19]([O-:21])=[O:20])=[CH:23][CH:24]=1)=[O:13]

Participants

6

Reactant 3

HCID 9804-NitrophenolHCID 24386Thionyl ChlorideHCID 57249691HCID 57249691, compound

Product 1

HCID 86672959HCID 86672959, compoundYield 77.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

To a 1 L flask was added toluene (500 mL), 2-(2-fluorophenyl)propanedioic acid (100 g, 0.479 moles) and N,N-dimethylformamide (6.92 g) at 25° C. under a nitrogen atmosphere. The reaction mixture was initially heated to 30° C. and thionyl chloride (127.53 g, 1.071 moles) was added dropwise over a period of 20 minutes at 25-30° C. After the addition, the reaction mixture was heated to 48-50° C. and this temperature maintained for 3.5 hours. Toluene (300 mL) was then added to the reaction mixture in one portion, followed by the addition of solid 4-nitrophenol (148.09 g total, 1.064 moles) in ten portions over a period of 15 minutes. After the addition, the reaction mixture was maintained at 49-55° C. for 1.5 hours. The reaction mixture was then concentrated under reduced pressure at 40-45° C. to remove toluene. The resulting residue was triturated using cold methanol (300 mL, approximately 5° C.) to yield an off-white solid which was isolated by filtration, washed with cold methanol (2×150 mL, approximately 5° C.) and dried under reduced pressure at 45° C. to give the title compound (163.8 g, 71.6%).

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was heated to 48-50° C.
  3. temperaturethis temperature maintained for 3.5 hours
  4. additionAfter the addition
  5. temperaturethe reaction mixture was maintained at 49-55° C. for 1.5 hours
  6. concentrationThe reaction mixture was then concentrated under reduced pressure at 40-45° C.
  7. customto remove toluene
  8. customThe resulting residue was triturated
  9. custommethanol (300 mL, approximately 5° C.)
  10. customto yield an off-white solid which
  11. customwas isolated by filtration
  12. washwashed with cold methanol (2×150 mL, approximately 5° C.)
  13. customdried under reduced pressure at 45° C.

Sources & evidence

ORD record
ord-f33545d6957d464d91870197316179c2
Source dataset
uspto-grants-2014_05
Patent number
US08722690B2

Reaction notes

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