Dichloromethane ethylacetate → 2-Chloro-5-fluoropyridin-4-amine

HRID 1061500Notes

Reaction equation

HRID 1061500 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([F:11])=[CH:4][N+:3]=1[O-].C(Cl)Cl.CCOC(C)=O>[Ni].C(O)C>[NH2:8][C:6]1[C:5]([F:11])=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=1

Participants

5

Reactant 2

HCID 21226138Dichloromethane ethylacetateHCID 222840222-Chloro-5-fluoro-4-nitro-1-oxo-1lambda~5~-pyridine

Product 1

HCID 222840352-Chloro-5-fluoropyridin-4-amineYield 91%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

A mixture of 2-chloro-5-fluoro-4-nitropyridine-1-oxide (11, 1.3 g, 6.8 mmol) and 1.6 g of Raney nickel in 80 mL of anhydrous ethyl alcohol was hydrogenated at 40 psi in a Parr hydrogenation apparatus for 3 h when TLC showed that the starting material had disappeared and a new spot was detected (CH2Cl2/EtOAc, 4:1, v/v, Rf0.78 and 0.71, for the starting material and the product, respectively). The catalyst was removed by filtration and washed carefully with ethyl alcohol. The filtrate and washings were combined and evaporated in vacuo to give 0.9 g (91%) of product as an off-white solid. A small analytical sample was purified by recrystallization from hot water to afford white crystals: mp 110-111° C.; 1H NMR (CDCl3) δ4.50 (br s, 2 H, NH2, D2O exchangeable), 7.15 (d, 1 H, 3-H, J=6 Hz), 7.95 (d, 1H, 6-H, J=2 Hz). Analysis calculated for C5H4ClFN2: C, 40.97; H, 2.75; N, 19.12. Found: C, 41.18; H, 2.39; N, 18.89.

Workup

  1. customThe catalyst was removed by filtration
  2. washwashed carefully with ethyl alcohol
  3. customevaporated in vacuo

Sources & evidence

ORD record
ord-24e236fa91f74f8cb09f083efcc9a204
Source dataset
uspto-grants-2005_11
Patent number
US06960568B2

Reaction notes

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