Sodium Iodide → HCID 178516121, compound

HRID 1623232Notes

Reaction equation

HRID 1623232 reaction equation
[F:1][C:2]1[C:3]([NH:10][CH2:11][CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[N:4][C:5]([O:8]C)=[CH:6][CH:7]=1.[I-].[Na+].[Si](Cl)(C)(C)C>C(#N)C.CCOC(C)=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[N:4][C:3]=1[NH:10][CH2:11][CH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

7

Reactant 3

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 669369273-fluoro-6-methoxy-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine

Product 1

HCID 178516121HCID 178516121, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 3-fluoro-6-methoxy-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (4.6 g, 19.14 mmol) in acetonitrile (50 mL) was added sodium iodide (20.09 g, 134 mmol) and TMS-chloride (17.13 mL, 134 mmol). The resulting mixture was stirred at about 95° C. for 20 hr. The reaction mixture was cooled to ambient temperature and then diluted with EtOAc (80 mL) and water (40 mL). The diluted mixture was stirred vigorously for about 30 min. The organic layer was separated and washed with 0.1N aqueous HCl solution. The combined aqueous layers were carefully neutralized (pH ˜7) with solid NaHCO3 solution and extracted with EtOAc (1×100 mL) and DCM (2×50 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=10/90 for 2 min, EtOAc/heptane=10/90 to 100/0 over 23 min, then EtOAc/heptane=100/0] providing 5-fluoro-6-((tetrahydro-2H-pyran-4-yl)methyl)aminopyridin-2-ol as a highly viscous oil which turned to purple upon standing at room temperature. Yield: 780 mg. LCMS (m/z): 227.1 [M+H]+; Retention time=0.42 min.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. stirringThe diluted mixture was stirred vigorously for about 30 min
  3. customThe organic layer was separated
  4. washwashed with 0.1N aqueous HCl solution
  5. extractionextracted with EtOAc (1×100 mL) and DCM (2×50 mL)
  6. washThe combined organic layers were washed with saturated aqueous NaHCO3 solution and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered off
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=10/90 for 2 min
  11. waitEtOAc/heptane=10/90 to 100/0 over 23 min

Sources & evidence

ORD record
ord-87882c2d7ea54e42b5aef56f8781382c
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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