Dimethylformamide → HCID 89445479, compound

HRID 1771688Notes

Reaction equation

HRID 1771688 reaction equation
[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:9][CH:8]=[C:7]([F:18])[C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:30][C:31]1[C:32]([F:39])=[C:33]([OH:38])[CH:34]=[CH:35][C:36]=1[F:37]>C(Cl)Cl.C1COCC1.O>[F:39][C:32]1[C:33]([OH:38])=[CH:34][CH:35]=[C:36]([F:37])[C:31]=1[NH:30][C:4](=[O:6])[C:3]1[C:7]([F:18])=[CH:8][CH:9]=[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[C:2]=1[F:1]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 227559833-Amino-2,4-difluorophenolHCID 89444396HCID 89444396, compound

Product 1

HCID 89445479HCID 89445479, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2,6-difluoro-3-(3-fluorophenyl)benzoic acid (765 mg, 3.03 mmol, 1.1 eq) and oxalyl chloride (1.05 g, 8.5 mmol, 3.0 eq) in DCM (20 mL) was added DMF (0.1 mL). The reaction mixture was stirred at room temperature for 2 h, then concentrated in vacuo. The residue obtained was dissolved in THF (5 mL) and added dropwise to a solution of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (400 mg, 2.76 mmol, 1.0 eq) in THF (25 mL) at 0° C. over 10 min. After addition, the reaction mixture was allowed to warm to room temperature and stirred for 3 h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound as a yellow solid (600 mg, 61%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue obtained
  3. additionAfter addition
  4. temperatureto warm to room temperature
  5. stirringstirred for 3 h
  6. extractionextracted with EtOAc
  7. extractionThe organic extract
  8. washwas washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. custompurified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4)

Sources & evidence

ORD record
ord-049a14c15e56454187648c2a0f17d683
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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