Sodium hydride → HCID 67261866, compound

HRID 2368792Notes

Reaction equation

HRID 2368792 reaction equation
[F:1][C:2]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:3]=1[CH2:4][C:5]1[CH:6]=[C:7]([I:12])[C:8](=[O:11])[NH:9][CH:10]=1.[H-].[Na+].[F:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23]Br>CN(C=O)C>[F:1][C:2]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:3]=1[CH2:4][C:5]1[CH:6]=[C:7]([I:12])[C:8](=[O:11])[N:9]([CH2:23][C:22]2[CH:25]=[CH:26][CH:27]=[CH:28][C:21]=2[F:20])[CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67968alpha-Bromo-o-fluorotolueneHCID 67260294HCID 67260294, compound

Product 1

HCID 67261866HCID 67261866, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 5-(2,4-difluorobenzyl)-3-iodopyridin-2(1H)-one 4 (5.58 g, 16.1 mmol) in anhydrous DMF (160 ml) was added at room temperature NaH (60% suspension in mineral oil, 0.71 g, 17.7 mmol). After the mixture was stirred for 15 min, o-fluorobenzyl bromide (2 ml, 16.1 mmol) was added to the mixture, which was stirred for 2 h at RT. The solvent was distilled off and the residue was dissolved in ethyl acetate (200 ml), washed with water (200 ml), brine (200 ml), and dried over anhydrous sodium sulfate and the solvent was distilled off. The residue was purified by flash chromatography on silica gel (hexanes:ethyl acetate, 80:20). Yield 6.61 g (90%). 1H NMR (CDCl3, 500 MHz): δ 7.80 (d, 1H, J=2.2 Hz), 7.55-7.51 (m, 1H), 7.32-7.27 (m, 2H), 7.13-7.04 (m, 3H), 6.86-6.79 (m, 2H), 5.14 (s, 2H), 3.64 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 162.4, 162.1, 160.5, 160.2, 159.1, 149.8, 136.5, 132.1, 131.1, 130.3, 124.6, 122.5, 121.9, 118.6, 115.4, 111.5, 104.2, 93.5, 48.5, 30.0.

Workup

  1. stirringwas stirred for 2 h at RT
  2. distillationThe solvent was distilled off
  3. dissolutionthe residue was dissolved in ethyl acetate (200 ml)
  4. washwashed with water (200 ml), brine (200 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off
  7. customThe residue was purified by flash chromatography on silica gel (hexanes:ethyl acetate, 80:20)

Sources & evidence

ORD record
ord-779a605cd1784d21a243461f1f998c1d
Source dataset
uspto-grants-2014_04
Patent number
US08703801B2

Reaction notes

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