Methanol → 4-((4-Nitronaphthalen-1-yloxy)methyl)pyridin-3-amine

HRID 2067052Notes

Reaction equation

HRID 2067052 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH2:8][OH:9].[H-].[Na+].F[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([N+:23]([O-:25])=[O:24])=[CH:15][CH:14]=1.CO>C1COCC1>[N+:23]([C:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:13]([O:9][CH2:8][C:7]2[CH:6]=[CH:5][N:4]=[CH:3][C:2]=2[NH2:1])=[CH:14][CH:15]=1)([O-:25])=[O:24]

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 2617641-Fluoro-4-nitronaphthaleneHCID 14950620(3-Aminopyridin-4-yl)methanol

Product 1

HCID 584167624-((4-Nitronaphthalen-1-yloxy)methyl)pyridin-3-amineYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-amino-pyridin-4-yl)-methanol (5) (4.00 g, 32.2 mmol) in anhydrous THF (160 mL) at 0° C. was added sodium hydride (1.55 g, 38.7 mmol, 60 wt %). After stirring for 20 min, 1-fluoro-4-nitronaphthalene (6.16 g, 32.2 mmol) was added, the ice bath removed and the reaction mixture left to warm to RT and stir for 12 hr. The reaction mixture was partitioned between EtOAc (200 mL) and saturated aq NaHCO3 solution (150 mL). The remaining yellow solid was collected by filtration and washed sequentially with water (50 mL), MeOH (50 mL) and diethyl ether (100 mL) and was identified as the desired product by LC-MS and 1H NMR. The filtrate was returned to a separating funnel; the organic phase was collected and washed with brine (100 mL), dried and concentrated in vacuo to afford an orange residue. Trituration of the orange residue with MeOH (200 mL) afforded an orange solid which was washed with diethyl ether (200 mL). LC-MS and 1H NMR analysis of the orange solid were identical to that observed for the insoluble solid obtained earlier. The two products were combined to afford 4-((4-nitronaphthalen-1-yloxy)methyl)pyridin-3-amine (6) (7.80 g, 77%): m/z 296 (M+H)+ (ES+).

Workup

  1. customthe ice bath removed
  2. waitthe reaction mixture left
  3. stirringstir for 12 hr
  4. customThe reaction mixture was partitioned between EtOAc (200 mL) and saturated aq NaHCO3 solution (150 mL)
  5. filtrationThe remaining yellow solid was collected by filtration
  6. washwashed sequentially with water (50 mL), MeOH (50 mL) and diethyl ether (100 mL)
  7. customThe filtrate was returned to a separating funnel
  8. customthe organic phase was collected
  9. washwashed with brine (100 mL)
  10. customdried
  11. concentrationconcentrated in vacuo
  12. customto afford an orange residue
  13. washwas washed with diethyl ether (200 mL)
  14. customobtained earlier

Sources & evidence

ORD record
ord-23e414fc4b3a4d4f9e26a121aad92dde
Source dataset
uspto-grants-2012_10
Patent number
US08293748B2

Reaction notes

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