Sodium Iodide → [2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-[2-fluoro-5-(3-hydroxy-propoxy)-phenyl]-methanone

HRID 1012656Notes

Reaction equation

HRID 1012656 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][C:3]=1[C:17]([C:19]1[CH:24]=[C:23]([OH:25])[CH:22]=[CH:21][C:20]=1[F:26])=[O:18].Cl[CH2:28][CH2:29][CH2:30][OH:31].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>C(#N)C>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][C:3]=1[C:17]([C:19]1[CH:24]=[C:23]([O:25][CH2:28][CH2:29][CH2:30][OH:31])[CH:22]=[CH:21][C:20]=1[F:26])=[O:18]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 123133-Chloro-1-propanolHCID 67314403[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(2-fluoro-5-hydroxy-phenyl)-methanone

Product 1

HCID 58677626[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-[2-fluoro-5-(3-hydroxy-propoxy)-phenyl]-methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

Compound 512 (38 mg, 0.1 mmol) was dissolved in acetonitrile (2 mL) in a reaction vial. 3-Chloro-propan-1-ol (11 μL, 0.12 mmol), K2CO3 (17 mg, 0.12 mmol) and NaI (cat. amount) were added. The reaction vial was flushed with argon, closed and then stirred at 130° C. for 20 min. in a microwave oven. The reaction mixture was allowed to cool to RT and then poured into a mixture of EtOAc/water. The aqueous phase was acidified with HCl (4N) and the layers were separated. The aqueous phase was extracted with more EtOAc. The organic phases were combined, dried (MgSO4), filtered and concentrated in vacuo affording the crude product. Purified by continuously gradient flash chromatography using EtOAc/petroleum ether (40-60)(v:v=1:3 to 1:1) as the eluent, affording the title compound as a yellow solid. 13C NMR (CDCl3) δ 190.8, 159.1 (dd), 155.6 (dd), 155.3 (d), 155.0 (d), 148.0, 134.7, 133.0, 129.4, 127.9 (d), 124.4 (m), 120.4 (d), 117.1 (d), 116.0, 115.1 (d), 112.8, 111.6 (dd), 104.9 (dd), 66.3, 60.0, 32.0

Workup

  1. customThe reaction
  2. customvial was flushed with argon
  3. customclosed
  4. temperatureto cool to RT
  5. additionpoured into a mixture of EtOAc/water
  6. customthe layers were separated
  7. extractionThe aqueous phase was extracted with more EtOAc
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customaffording the crude product
  12. customPurified by continuously gradient flash chromatography

Sources & evidence

ORD record
ord-7229475fc31f4cca83fd0e0b41a86041
Source dataset
uspto-grants-2011_07
Patent number
US07977387B2

Reaction notes

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