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

HRID 1629130Notes

Reaction equation

HRID 1629130 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 (1 H, s), 7.20 (1 H, s), 3.86 (3 H, 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-90f47a48fca44a5c9d6519dfcaa71422
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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