Diisopropylethylamine → N-(3-bromo-2-methylphenyl)-2-(3-fluoropyridin-2-yl)acetamide

HRID 523267Notes

Reaction equation

HRID 523267 reaction equation
[F:1][C:2]1[C:3]([CH2:8][C:9]([O-:11])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.[Na+].[Br:13][C:14]1[C:15]([CH3:21])=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[Br:13][C:14]1[C:15]([CH3:21])=[C:16]([NH:17][C:9](=[O:11])[CH2:8][C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1235383-Bromo-o-toluidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117761161Sodium 2-(3-fluoropyridin-2-yl)acetate

Product 1

HCID 117760599N-(3-bromo-2-methylphenyl)-2-(3-fluoropyridin-2-yl)acetamideYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of sodium 2-(3-fluoropyridin-2-yl)acetate (1.847 g, 10.37 mmol), 3-bromo-2-methylaniline (1.41 mL, 11.4 mmol), DIEA (5.4 mL, 31.1 mmol) and HATU (4.73 g, 12.4 mmol) in DMF (30 mL) was stirred at room temperature for 1.25 h. The mixture was diluted with EtOAc and washed twice with 10% aqueous LiCl, then with brine. The combined aqueous layers were extracted with EtOAc, and the combined organic phases were dried and concentrated. The residue was dissolved in hot EtOAc, allowed to cool, and the resulting white solid collected by filtration and washed with 60% EtOAc-hexanes. The combined filtrates were concentrated and the residue was recrystallized twice using the same procedure. The residue from concentration of the final filtrate was purified by column chromatography on silica gel, eluting with EtOAc-hexanes, to provide a solid which was combined with the recrystallized batches to provide N-(3-bromo-2-methylphenyl)-2-(3-fluoropyridin-2-yl)acetamide as a white solid (2.03 g, 61% yield). Mass spectrum m/z 323, 325 (M+H)+.

Workup

  1. washwashed twice with 10% aqueous LiCl
  2. extractionThe combined aqueous layers were extracted with EtOAc
  3. customthe combined organic phases were dried
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in hot EtOAc
  6. temperatureto cool
  7. filtrationthe resulting white solid collected by filtration
  8. washwashed with 60% EtOAc-hexanes
  9. concentrationThe combined filtrates were concentrated
  10. customthe residue was recrystallized twice
  11. customThe residue from concentration of the final filtrate was purified by column chromatography on silica gel
  12. washeluting with EtOAc-hexanes
  13. customto provide a solid which

Sources & evidence

ORD record
ord-93c8117f856e4b19943456aa8af207ab
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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