Triethylamine → 6-fluoro-N-methoxy-N-methylpicolinamide

HRID 419211

Reaction equation

HRID 419211 reaction equation
[F:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.[CH3:11][NH:12][O:13][CH3:14].CCN(CC)CC.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(Cl)Cl>[CH3:14][O:13][N:12]([CH3:11])[C:8]([C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[N:7]=1)=[O:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14232N,O-DimethylhydroxylamineHCID 111923Propylphosphonic anhydrideHCID 2260276-Fluoropyridine-2-carboxylic acid

Product 1

HCID 597006206-fluoro-N-methoxy-N-methylpicolinamideYield 76.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled mixture of 6-fluoro picolinic acid (1.19 g, 8.43 mmol), N,O-dimethylhydroxylamine (860 mg, 8.82 mmol) and Et3N (3.27 mL, 23.52 mmol) in CH2Cl2 (10 mL) was added 1-propane phosphonic acid cyclic anhydride (4.49 mL, 7.05 mmol; 50 wt % solution in EtOAc) dropwise and stirred at room temperature for 3 h. The reaction mixture was filtered, washed with CH2Cl2 (2×10 mL), evaporated to dryness, and subjected to column chromatography (SiO2, 40% EtOAc-hexanes) to obtain 6-fluoro-pyridine-2-carboxylic acid methoxy-methyl-amide (1.19 g) in 73% yield. ESMS m/z (relative intensity): 185 (M+H)+ (100).

Workup

  1. filtrationThe reaction mixture was filtered
  2. washwashed with CH2Cl2 (2×10 mL)
  3. customevaporated to dryness

Sources & evidence

ORD record
ord-e6fa78f5e3dd418d8b31fdb90bd9e98e
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Linked notes

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