6-Chloronicotinic acid → 6-Chloro-N-methoxy-N-methylnicotinamide

HRID 537473Notes

Reaction equation

HRID 537473 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][N:3]=1.CN([C:14]([O:18][N:19]1N=NC2C=CC=C[C:20]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)CC)(C)C.Cl.COCN>CN(C=O)C.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:19]([O:18][CH3:14])[CH3:20])=[O:7])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 792226-Chloronicotinic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21959107Methoxymethanamine hydrochloride

Product 1

HCID 114355976-Chloro-N-methoxy-N-methylnicotinamideYield 90.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 6-chloronicotinic acid (2.0 g, 12.7 mmol) in DMF (20 mL) was added TBTU (6.11 g, 19.0 mmol), di-iso-propylethylamine (4.9 g, 38.1 mmol), and N-methoxymethylamine hydrochloride (1.48 g, 15.2 mmol). The reaction mixture was stirred at 25° C. overnight. The reaction solution was poured into brine (40 mL) and extracted with ethyl acetate (40 mL*2). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography to give 6-chloro-N-methoxy-N-methylnicotinamide (2.3 g) as an oil. 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J=2.0 Hz, 1H), 7.95 (dd, J=2.4, 8.4 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 3.49 (s, 3H), 3.32 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (40 mL*2)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b2a95619d93c46219b57a39b9341d37a
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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