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

HRID 1664167Notes

Reaction equation

HRID 1664167 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 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) δppm: 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.

Workup

  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

Sources & evidence

ORD record
ord-9cb188ef23b84868bd27f3fd2bfad8da
Source dataset
uspto-grants-2011_10
Patent number
US08039458B2

Reaction notes

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