Trifluoroacetic acid → 4-Chloro-5-iodo-2-methoxypyridine

HRID 2044320Notes

Reaction equation

HRID 2044320 reaction equation
[Cl:1][C:2]1[C:7]([I:8])=[CH:6][N:5]=[C:4](N)[CH:3]=1.[C:10](O)(C(F)(F)F)=[O:11].N(OC(C)(C)C)=O>CO>[Cl:1][C:2]1[C:7]([I:8])=[CH:6][N:5]=[C:4]([O:11][CH3:10])[CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 10906Tert-Butyl nitriteHCID 219491214-Chloro-5-iodopyridin-2-amine

Product 1

HCID 582045954-Chloro-5-iodo-2-methoxypyridineYield 92.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-chloro-5-iodo-pyridin-2-ylamine (64.2 g, 0.25 mol) in methanol (1.1 L) and TFA (93.7 mL, 1.26 mol) was added tert-butyl nitrite (150 mL, 1.26 mol) so as to maintain temperature less than 3° C. The resultant mixture was stirred at RT for 1 h then allowed to warm to RT and stirred for 16 h. The reaction was quenched by the careful addition of water then concentrated in vacuo to ¼ volume. The resultant residue was treated with water (1 L) and the precipitate formed collected by filtration and dried in vacuo at 35° C. to give the title compound (62.3 g, 92%). Contains 16% impurity. 1H NMR 400 MHz (DMSO-d) δ: 8.56 (1H, s), 7.20 (1H, s), 3.86 (3H, s).

Workup

  1. temperatureto maintain temperature less than 3° C
  2. customThe reaction was quenched by the careful addition of water
  3. concentrationthen concentrated in vacuo
  4. additionThe resultant residue was treated with water (1 L)
  5. customthe precipitate formed
  6. filtrationcollected by filtration
  7. customdried in vacuo at 35° C.

Sources & evidence

ORD record
ord-dcde058d55a04e0e98445e8f56d8928d
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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