Water → 2-((4-Fluoro-3-nitrophenoxy)methyl)quinoline

HRID 2178432Notes

Reaction equation

HRID 2178432 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].Cl[CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:13][C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 203942-(Chloromethyl)quinolineHCID 167518614-Fluoro-3-nitrophenol

Product 1

HCID 904169762-((4-Fluoro-3-nitrophenoxy)methyl)quinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-fluoro-3-nitrophenol (8.1 g, 38 mmol) and 2-(chloromethyl)quinoline (6.0 g, 38 mmol) in DMF (100 mL) were added K2CO3 (21 g, 153 mmol) followed by KI (317 mg, 1.9 mmol). The mixture was stirred at 50° C. for 5 h. The mixture was cooled to RT, water (100 mL) was added, and the mixture was extracted with EtOAc (3×150 mL). The organics were combined, washed with brine (50 mL), dried (Na2SO4), filtered and concentrated to dryness. The residue was purified by FCC to afford the title compound. 1H NMR (300 MHz, CDCl3) δ 8.27 (d, J=9, 1H), 8.15 (d, J=9, 1H), 7.87 (d, J=9, 1H), 7.80-7.72 (m, 2H), 7.65-7.56 (m, 2H), 7.32-7.26 (m, 1H), 7.23-7.16 (m, 1H), 5.44 (s, 2H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. extractionthe mixture was extracted with EtOAc (3×150 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-1ccf6c2633cb4decb2c443296b3448f8
Source dataset
uspto-grants-2015_06
Patent number
US09067917B2

Reaction notes

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