Triethylamine → 3-Fluoro-5-bromopyridine carboxylic acid methoxymethylamide

HRID 873318Notes

Reaction equation

HRID 873318 reaction equation
Cl.[F:2][C:3]1[C:4]([C:10]([OH:12])=O)=[N:5][CH:6]=[C:7]([Br:9])[CH:8]=1.CC[N:15]([CH2:18]C)CC.CN([C:23]([O:27]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:23][O:27][CH2:18][NH:15][C:10]([C:4]1[C:3]([F:2])=[CH:8][C:7]([Br:9])=[CH:6][N:5]=1)=[O:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 709788255-Bromo-3-fluoropicolinic acid hydrochloride

Product 1

HCID 684519843-Fluoro-5-bromopyridine carboxylic acid methoxymethylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 3-fluoro-5-bromopyridine carboxylic acid hydrochloride (1.83 g, 6.5 mmol), N—O-dimethyl hydroxylamine hydrochloride (824 mg, 8.45 mmol), Et3N (2.3 mL, 16.25 mmol) and HATU (3.2 g, 8.45 mmol) in dry DMF (30 mL) was stirred at room temperature under N2 for 16 h. Further HATU (900 mg, 2.4 mmol) was added and the reaction stirred for a further 6 h. The solvent was removed in vacuo and the crude partitioned between saturated NaHCO3 (aq) and EtOAc. The aqueous was extracted with additional EtOAc (×3) and the combined organics washed with brine dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (gradient: 20%-80% EtOAc in petroleum ether 40-60:EtOAc) yielded 3-fluoro-5-bromopyridine carboxylic acid methoxymethylamide as a yellow solid.

Workup

  1. stirringthe reaction stirred for a further 6 h
  2. customThe solvent was removed in vacuo
  3. customthe crude partitioned between saturated NaHCO3 (aq) and EtOAc
  4. extractionThe aqueous was extracted with additional EtOAc (×3)
  5. washthe combined organics washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (gradient: 20%-80% EtOAc in petroleum ether 40-60:EtOAc)

Sources & evidence

ORD record
ord-d7be5184f52d4d3d88f4bd70858fc32d
Source dataset
uspto-grants-2015_03
Patent number
US08975406B2

Reaction notes

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