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

HRID 1530464Notes

Reaction equation

HRID 1530464 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 one-fourth of the 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-d6) 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 to one-fourth of the volume
  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-0687d4c81f234d2793775b5e929d02ec
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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