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

HRID 432299노트

반응식

HRID 432299 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-3f4c550f67f144839dff084a50b68191
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06660744B1

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