Sodium Iodide → HCID 58882977, compound

HRID 2364196Notes

Reaction equation

HRID 2364196 reaction equation
[NH2:1][C:2]1[C:3]([C:16]([O:18][CH3:19])=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[CH:7]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C([O-])(O)=O.[Na+].C([O-])([O-])=O.[K+].[K+].[Na+].[I-].Cl[CH2:47][C:48]([N:50]([CH3:52])[CH3:51])=[O:49]>C(OC(C)=O)(C)C.CO>[CH3:51][N:50]([CH3:52])[C:48](=[O:49])[CH2:47][NH:1][C:2]1[C:3]([C:16]([O:18][CH3:19])=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=2)[CH:7]=1

Participants

9

Reactant 6

HCID 5238Sodium IodideHCID 9845Trifluoroacetic anhydrideHCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 516892Sodium BicarbonateHCID 58882991Methyl 3-amino-5-[(4-fluorophenyl)methyl]pyridine-2-carboxylate

Product 1

HCID 58882977HCID 58882977, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

A stirring suspension of methyl 3-amino-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (60 g, 0.23 mol) in i-PrOAc (400 mL) was heated to 30° C. and trifluoroacetic anhydride (35.3 mL, 0.254 mol) was added dropwise. The reaction mixture was stirred 15 min at 30° C.; then cooled to rt and quenched slowly with 0.6 M NaHCO3 solution (512 mL, 0.32 mol). The resulting biphasic mixture was separated and the organic phase was washed twice with water; then diluted with CH3CN (700 mL) and distilled to about half its initial volume. To the remaining solution (ca. 600 mL) was added K2CO3 (34.6 g, 0.255 mol), NaI (5.18 g, 34.6 mol) and 2-chloro-N,N-dimethylacetamide (26.1 mL, 0.254 mol) and the resulting mixture was heated to 80° C. for 3.5 h. The reaction was cooled to 60° C., diluted with MeOH (200 mL), heated at reflux for 2 h and then distilled to approximately half its original volume. The remaining mixture was cooled to 37° C. and water (650 mL) was added over 2 h with gradual cooling to 15° C. A precipitate formed which was collected by filtration and washed with water. Drying of the filter cake in a vacuum oven afforded the product as an off-white solid: 1H NMR (CDCl3) δ 8.56 (1H, br), 7.89 (1H, s), 7.12 (2H, dd, J=8.5, 5.5 Hz), 6.98 (2H, t, J=8.5 Hz), 6.68 (1H, s), 3.96 (3H, s), 3.93 (2H, s), 3.88 (2H, d, J=4.2 Hz), 3.02 (3H, s), 3.01 (3H, s).

Workup

  1. temperaturethen cooled to rt
  2. customThe resulting biphasic mixture was separated
  3. washthe organic phase was washed twice with water
  4. additionthen diluted with CH3CN (700 mL)
  5. distillationdistilled to about half its initial volume
  6. temperaturethe resulting mixture was heated to 80° C. for 3.5 h
  7. temperatureThe reaction was cooled to 60° C.
  8. temperatureheated
  9. temperatureat reflux for 2 h
  10. distillationdistilled to approximately half its original volume
  11. temperatureThe remaining mixture was cooled to 37° C.
  12. additionwater (650 mL) was added over 2 h
  13. temperaturewith gradual cooling to 15° C
  14. customA precipitate formed which
  15. filtrationwas collected by filtration
  16. washwashed with water
  17. customDrying of the filter cake in a vacuum oven

Sources & evidence

ORD record
ord-eefee5e462b244299250e4978d9feb6c
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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