Sodium hydride → 4-Fluoro-2-(2-morpholino-2-oxoethoxy)benzonitrile

HRID 348162노트

반응식

HRID 348162 반응식
[F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([OH:10])[CH:3]=1.[H-].[Na+].Cl[CH2:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=[O:16]>CN(C)C=O>[F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:14][C:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])[CH:3]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 74040Morpholine, 4-(chloroacetyl)-HCID 110299014-Fluoro-2-hydroxybenzonitrile

생성물 1

HCID 210698914-Fluoro-2-(2-morpholino-2-oxoethoxy)benzonitrile수율 83.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of intermediate 129, 4-fluoro-2-hydroxybenzonitrile, (685 mg, 5 mmol) in dimethylformamide (8 mL, Sure Seal; Aldrich) was added NaH (200 mg, 5 mmol; 60% oil dispersion; Aldrich), and the mixture stirred for 5 min under an anhydrous nitrogen atmosphere. To this was added 4-(2-chloroacetyl)morpholine (900 mg, 5.5 mmol, 1.1 eq.; Avocado Organics), and stirring continued at room temperature for 21 hrs. The reaction was quenched by careful addition of water (30 mL). The resulting mixture was extracted with CH2Cl2 (25 mL×2). The combined extracts were washed with brine, dried (MgSO4) and concentrated. The residue was triturated to obtain 1.10 g (4.17 mmol, Yield 83%) of the title compound as a white solid: 1H NMR (CDCl3, 500 MHz) δ ppm: 3.63 (2H, t, J=4 Hz, NCH2), 3.67 (1H, m, OCH), 3.72 (1H, m, OCH), 4.86 (2H, s, OCH2), 6.80–6.86 (2H, m, Ar—Hs), 7.61 (1H, dd, J=8.5 Hz, 6.1 Hz, Ar—H); 13C NMR (CDCl3, 125.77 Hz) δ ppm: 42.63, 46.04, 66.80, 68.33, 98.45, 98.47, 101.57, 101.79, 109.56, 109.74, 115.42, 135.48, 135.57, 161.26, 161.35, 114.79, 165.23, 167.28. HRMS calcd for C13H14N2O3F (M+H) 265.0988, found 265.0998.

후처리

  1. stirringstirring
  2. waitcontinued at room temperature for 21 hrs
  3. customThe reaction was quenched by careful addition of water (30 mL)
  4. extractionThe resulting mixture was extracted with CH2Cl2 (25 mL×2)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was triturated

출처 및 근거

ORD 기록
ord-495ae570ab874d5eb73d339cf7c25391
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07176196B2

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