Picolinic acid → N-[4-(benzyloxy)phenyl]pyridine-2-carboxamide

HRID 1807817Notes

Reaction equation

HRID 1807817 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.[CH2:44]([O:51][C:52]1[CH:58]=[CH:57][C:55]([NH2:56])=[CH:54][CH:53]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH2:44]([O:51][C:52]1[CH:53]=[CH:54][C:55]([NH:56][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[O:9])=[CH:57][CH:58]=1)[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

7

Reactant 5

HCID 1018Picolinic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27238314-Benzyloxyaniline hydrochlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 2425421N-[4-(benzyloxy)phenyl]pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of pyridine-2-carboxylic acid (2.0 g, 8.48 mmol) in N,N-dimethylformamide (DMF) was treated with O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (3.5 g, 9.33 mmol) and N,N-diisopropylethylamine (DIEA) (0.742 mL, 32.7 mmol) and stirred at room temperature for 10 min. 4-Benzyloxyaniline hydrochloride (2.0 g, 8.48 mmol) was added to the solution, and stirring was continued for an additional 30 min. The solution was poured into a saturated aqueous solution of sodium bicarbonate on ice. Mechanically mixing the gummy residue in the bottom of the flask caused it to solidify. The product was collected by filtration, washed with water and dried to give a beige solid, 2.46 g (95%), which was used without further purification in the subsequent reaction. MS m/z 305 (MH+). 1H NMR(CDCl3) δ 5.07 (s, 2H), 7.0 (d, 2H), 7.30-7.50 (m, 6H), 7.70 (d, 2H), 7.92 (t, 1H), 8.32 (d, 1H) and 8.58 (d, 1H).

Workup

  1. stirringstirring
  2. waitwas continued for an additional 30 min
  3. additionMechanically mixing the gummy residue in the bottom of the flask
  4. filtrationThe product was collected by filtration
  5. washwashed with water
  6. customdried
  7. customto give a beige solid, 2.46 g (95%), which
  8. customwas used without further purification in the subsequent reaction

Sources & evidence

ORD record
ord-bc3c9eabcf384655ab83134ad580ae2a
Source dataset
uspto-grants-2013_01
Patent number
US08357715B2

Reaction notes

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