Hydrochloric Acid → N-(5-benzyl-2-hydroxyphenyl)-2-fluoro-4-formylbenzamide

HRID 2075249Notes

Reaction equation

HRID 2075249 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([CH:11]=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.[NH2:28][C:29]1[CH:34]=[C:33]([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:32]=[CH:31][C:30]=1[OH:42].Cl>C(Cl)Cl.CN(C)C=O.O.CCOC(C)=O>[CH2:35]([C:33]1[CH:32]=[CH:31][C:30]([OH:42])=[C:29]([NH:28][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][C:9]([CH:11]=[O:12])=[CH:10][C:2]=2[F:1])[CH:34]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 65578Oxalyl chloride2×HCID 81531DiisopropylethylamineHCID 2650022-Amino-4-benzylphenolHCID 184419582-Fluoro-4-formylbenzoic acid

Product 1

HCID 59651828N-(5-benzyl-2-hydroxyphenyl)-2-fluoro-4-formylbenzamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-fluoro-4-formylbenzoic acid (0.600 g, 3.57 mmol) in 15 mL DCM was added oxalyl dichloride (0.374 mL, 4.28 mmol) and N,N-dimethylformamide (0.00261 g, 0.0357 mmol) (a few drops). The mixture was allowed to stir for several h, treated with additional (COCl)2 (0.100 mL), stirred further for 1 h, concentrated in vacuo, and the semi-solid was suspended in 15 mL THF. N,N-diisopropylethylamine (0.808 mL, 4.64 mmol) was added followed by 2-amino-4-benzylphenol (0.711 g, 3.57 mmol). After 4 h, the reaction was treated with EtOAc, water, and 1N HCl. The organic layer was washed 1× brine, dried over sodium sulfate, filtered, and concentrated. The material was purified by silica gel chromatography to give title compound as a solid. MS (ESI) m/z: Calculated: 349.1; Observed: 347.7 (M−−1).

Workup

  1. stirringstirred further for 1 h
  2. concentrationconcentrated in vacuo
  3. washThe organic layer was washed 1× brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ac463e930641489c99e29d42d1397b62
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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