Sodium Iodide → 2-Iodo-4-[3-(trifluoromethoxy)phenyl]pyridine

HRID 624301Notes

Reaction equation

C(Cl)(=O)C.Cl[C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:22])([F:21])[F:20])[CH:13]=2)[CH:9]=[CH:8][N:7]=1.[I-:23].[Na+].C(=O)([O-])[O-].[Na+].[Na+].S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>CC#N.CCOC(C)=O.O>[I:23][C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:22])([F:21])[F:20])[CH:13]=2)[CH:9]=[CH:8][N:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Acetyl chloride (4.45 mL, 62.6 mmol) was added to a solution of 2-chloro-4-[3-(trifluoromethoxy)phenyl]-pyridine [CAS 1261856-64-7] (11.42 g, 41.73 mmol) and sodium iodide (31.28 g, 208.67 mmol) in MeCN (200 mL) under N2, and the resulting suspension was heated at 80° C. for 18 hrs. Additional sodium iodide was added (20 mol %) and stirring was continued for 3 hrs. The reaction was cooled and the mixture was treated with aqueous sodium carbonate. After 5 minutes, solid sodium metabisulphite was added until decolourisation achieved. Water was added to redissolve a precipitate which had formed. The mixture was diluted with EtOAc and the layers separated. The aqueous layer was washed with EtOAc (2×), the combined organics were dried (MgSO4) and the solvent evaporated to afford the crude 2-iodo-4-[3-(trifluoromethoxy)phenyl]pyridine (D9) (16.3 g) as a amber oil containing about ˜5% of reduced 2-H material and ˜8% of unreacted chloride starting material;

Workup

temperatureThe reaction was cooled
waitAfter 5 minutes
dissolutionto redissolve a precipitate which
customhad formed
customthe layers separated
washThe aqueous layer was washed with EtOAc (2×)
dry with materialthe combined organics were dried (MgSO4)
customthe solvent evaporated

Sources & evidence

ORD record: ord-cc585df640b14d5da4ce1e9fc10df379
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09303032B2

Reaction notes

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