Sodium hydride → 4-(1-(4-Nitronaphthalen-1-yloxy)ethyl)pyridin-2-amine

HRID 872410Notes

Reaction equation

HRID 872410 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH:8]([OH:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.[H-].[Na+].F[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([N+:24]([O-:26])=[O:25])=[CH:16][CH:15]=1>CN(C=O)C>[N+:24]([C:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:14]([O:10][CH:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=2)[CH3:9])=[CH:15][CH:16]=1)([O-:26])=[O:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2617641-Fluoro-4-nitronaphthaleneHCID 179991481-(2-Aminopyridin-4-yl)ethanol

Product 1

HCID 584167824-(1-(4-Nitronaphthalen-1-yloxy)ethyl)pyridin-2-amineYield 57.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 1-(2-aminopyridin-4-yl)ethanol (22) (73 mg, 0.528 mmol) in DMF (1.5 mL), under nitrogen at 0° C., was added sodium hydride (32 mg, 0.793 mmol, 60 wt %). The resulting mixture was stirred at 0° C. for 40 min, and a solution of 1-fluoro-4-nitronaphthalene (101 mg, 0.528 mmol) in DMF (1.5 mL) was added dropwise. The resulting dark-red mixture was stirred at 0° C. for a further 5 min, and then at RT. After a further 40 min, the reaction was quenched by the addition of 1.0 mL of NH4Cl solution. Water (20 mL) and EtOAc (20 mL) were added, and the layers were separated. The aqueous layer was extracted with EtOAc (15 mL×3). The combined organic extracts were washed with brine, dried and the solvents removed under reduced pressure. The crude material was purified by column chromatography (12 g), eluting with 0 to 80% EtOAc in iso-hexane, to give 4-(1-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-2-amine (23) (94.6 mg, 57%) as an orange gum: m/z 310 (M+H)+ (ES+).

Workup

  1. stirringThe resulting dark-red mixture was stirred at 0° C. for a further 5 min
  2. customat RT
  3. waitAfter a further 40 min
  4. customthe reaction was quenched by the addition of 1.0 mL of NH4Cl solution
  5. additionWater (20 mL) and EtOAc (20 mL) were added
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with EtOAc (15 mL×3)
  8. washThe combined organic extracts were washed with brine
  9. customdried
  10. customthe solvents removed under reduced pressure
  11. customThe crude material was purified by column chromatography (12 g)
  12. washeluting with 0 to 80% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-dd3001ac30e04e4f9e6ec86ea82299f1
Source dataset
uspto-grants-2015_03
Patent number
US08975285B2

Reaction notes

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