Water → 2-Fluoro-6-[(2-methoxyethyl)amino]benzonitrile

HRID 432299Notes

Reaction equation

HRID 432299 reaction equation
F[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].COC[CH2:14][CH2:15][NH2:16].[C:17](=[O:20])([O-])[O-].[K+].[K+].O>CN(C)C=O>[F:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([NH:16][CH2:15][CH2:14][O:20][CH3:17])[C:3]=1[C:4]#[N:5]

Participants

6

Reactant 4

HCID 962WaterHCID 16723-MethoxypropylamineHCID 11430Potassium CarbonateHCID 746952,6-Difluorobenzonitrile

Product 1

HCID 223466972-Fluoro-6-[(2-methoxyethyl)amino]benzonitrileYield 71.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2,6 difluorobenzonitrile (3.5 g, 25.16 mmol) in dimethylformamide (50 mL) was treated with 3-methoxypropylamine (2.24 g, 25.16 mmol) and potassium carbonate (6.94 g, 50.32 mmol). The reaction mixture was stirred over night under a nitrogen atmosphere. Water (100 mL) was added to the reaction solution. The layers were partitioned, and the aqueous layer was extracted with ethyl acetate (1.2 L). The combined organic layers were washed with water (1.5 L), dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel using 7:1 heptane:ethyl acetate as the eluent. The column afforded 3.5 g (68%) of 2-fluoro-6-[(2-methoxyethyl)amino]benzonitrile. 1H NMR (DMSO-d6, 400 MHz) δ 7.48-7.39 (m, 1H), 6.64-6.48 (m, 2H), 3.45-3.31 (m, 2H), 3.30-3.20 (m, 5H), 1.85-1.75 (m, 2H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 6.57 min (97%).

Workup

  1. customThe layers were partitioned
  2. extractionthe aqueous layer was extracted with ethyl acetate (1.2 L)
  3. washThe combined organic layers were washed with water (1.5 L)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by flash chromatography on silica gel using 7:1 heptane

Sources & evidence

ORD record
ord-3f4c550f67f144839dff084a50b68191
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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