5-Fluoro-2-nitrophenol → 350672-95-6

HRID 1428915Notes

Reaction equation

HRID 1428915 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.[H-].[Na+].Cl[CH2:15][O:16][CH2:17]Cl>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([O:8][CH2:15][O:16][CH3:17])[CH:7]=1

Participants

5

Reactant 3

HCID 99375-Fluoro-2-nitrophenolHCID 10967Bis(Chloromethyl) EtherHCID 24758Sodium hydride

Product 1

HCID 16085402350672-95-6Yield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Fluoro-2-nitrophenol (10 g, 63 mmol, 99%) was dissolved in anhydrous DMF (100 mL) in an oven-dried flask. The solution was stirred under an atmosphere of nitrogen and cooled in an ice-water bath. Sodium hydride (3.0 g, 75 mmol) was added with stirring, after which chloro methylether (5.3 g, 66 mmol) was added dropwise. The resulting mixture was aged at room temperature for 1 h. The reaction was quenched with MeOH, diluted with ether and washed with water and brine. The ether layer was dried over anhydrous Na2SO4 and concentrated in vacuo. Purification of the product by silica gel chromatography (hexanes/EtOAc=1/7) gave the title compound in 88% yield. 1H NMR (500 MHz, CDCl3) δ 3.53 (s, 3H), 5.30 (d, J=2.0 Hz, 2H), 6.78 (dd, J=7.3, 9.1 Hz, 1H), 7.06 (dt, J=2.3, 10.4 Hz, 1H), 7.91 (dd, J=6.0, 9.0 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 57.0, 95.6, 105.0 (d, J=26.3 Hz), 108.8 (d, J=23.0 Hz), 127.8 (d, J=10.7 Hz), 152.8 (d, J=11.5 Hz), 165.5 (d, J=255.9 Hz). HRMS (FAB) calcd for C8H8FNNaO4 (M+Na+) 224.0330. found 224.0328.

Workup

  1. temperaturecooled in an ice-water bath
  2. stirringwith stirring
  3. customThe reaction was quenched with MeOH
  4. additiondiluted with ether
  5. washwashed with water and brine
  6. dry with materialThe ether layer was dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification of the product by silica gel chromatography (hexanes/EtOAc=1/7)

Sources & evidence

ORD record
ord-40ed55aea24a4fc8907c5c47d97ab5d5
Source dataset
uspto-grants-2015_01
Patent number
US08937151B2

Reaction notes

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