4-Fluoroaniline → N-(4-Fluorophenyl)-5-methyl-2-furanacetamide

HRID 2378396Notes

Reaction equation

HRID 2378396 reaction equation
[CH3:1][C:2]1[O:6][C:5]([CH2:7][C:8]([OH:10])=O)=[CH:4][CH:3]=1.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.[F:32][C:33]1[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=1>CC#N.CN(C=O)C.CCOC(C)=O>[F:32][C:33]1[CH:39]=[CH:38][C:36]([NH:37][C:8](=[O:10])[CH2:7][C:5]2[O:6][C:2]([CH3:1])=[CH:3][CH:4]=2)=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 97314-FluoroanilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 1558752-Furanacetic acid, 5-methyl-HCID 181649HOAt

Product 1

HCID 21874934N-(4-Fluorophenyl)-5-methyl-2-furanacetamideYield 95%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21891449acetonitrile N,N-dimethylformamideSolvent

Procedure

5-Methyl-2-furanacetic acid (1.00 g, 7.14 mmol, synthesized as described WO 9507893, Example 19) was dissolved in CH3CN/DMF (4:1, 25 mL), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (1.37 g, 7.14 mmol) and 1-hydroxy-7-azabenzotriazole (0.972 g, 7.14 mmol) were then added followed by 4-fluoroaniline (0.676 mL, 7.14 mmol). After 3 h, the reaction was diluted with EtOAc (150 mL) and washed with 1 N HCl (1×30 mL), sat. aq. NaHCO3 (1×30 mL), brine (1×40 mL) and dried over sodium sulfate. Compound 216A (1.58 g, 95%)) was isolated as a yellow foam after concentration in vacuo. No further purification was necessary. HPLC: 78% at 2.647 min (retention time) (YMC S5 ODS column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).

Workup

  1. washwashed with 1 N HCl (1×30 mL), sat. aq. NaHCO3 (1×30 mL), brine (1×40 mL)
  2. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-f0c450c8f0994154ba2238db07c91d38
Source dataset
uspto-grants-2008_12
Patent number
US07470797B2

Reaction notes

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