Acetic Acid → 3-(2,6-Dichloro-3-fluoro-benzyloxy)-pyridin-2-ylamine

HRID 1627513Notes

Reaction equation

HRID 1627513 reaction equation
CC(O)=O.CCO.[Cl:8][C:9]1[C:25]([F:26])=[CH:24][CH:23]=[C:22]([Cl:27])[C:10]=1[CH2:11][O:12][C:13]1[C:14]([N+:19]([O-])=O)=[N:15][CH:16]=[CH:17][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Fe].O.C(OCC)C>[Cl:8][C:9]1[C:25]([F:26])=[CH:24][CH:23]=[C:22]([Cl:27])[C:10]=1[CH2:11][O:12][C:13]1[C:14]([NH2:19])=[N:15][CH:16]=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 702EthanolHCID 10340Sodium CarbonateHCID 211113993-(2,6-Dichloro-3-fluoro-benzyloxy)-2-nitro-pyridine

Product 1

HCID 211114003-(2,6-Dichloro-3-fluoro-benzyloxy)-pyridin-2-ylamineYield 99%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

To a stirred mixture of AcOH (650 mL) and EtOH (500 mL) was suspended 3-(2,6-dichloro-3-fluoro-benzyloxy)-2-nitro-pyridine (9.43 g, 0.028 mol) and iron chips (15.7 g, 0.28 mol). The reaction was heated slowly to reflux and allowed to stir for 1 hr. The reaction was cooled to room temperature then diethyl ether (500 mL) and water (500 mL) was added. The solution was carefully neutralized by the addition of sodium carbonate. The combined organic extracts were washed with sat'd NaHCO3 (2×100 mL), H2O (2×100 mL) and brine (1×100 mL) then dried (Na2SO4), filtered and concentrated to dryness under vacuum to yield 3-(2,6-dichloro-3-fluoro-benzyloxy)-pyridin-2-ylamine (9.04 g, 0.027 mol, 99%) as a light pink solid. 1H NMR (CDCl3, 300 MHz) δ1.8-1.85 (d, 3H), 4.9-5.2 (brs, 2H), 6.7-6.84 (q, 1H), 7.0-7.1 (m, 1H), 7.2-7.3 (m, 1H), 7.6-7.7 (m, 1H).

Workup

  1. temperatureThe reaction was heated slowly
  2. temperatureto reflux
  3. washThe combined organic extracts were washed with sat'd NaHCO3 (2×100 mL), H2O (2×100 mL) and brine (1×100 mL)
  4. dry with materialthen dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under vacuum

Sources & evidence

ORD record
ord-0b29d1e6d4ac4673acf9de4f99bff8b2
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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