2-Fluoronicotinic acid → HCID 57721337, compound

HRID 1986086Notes

Reaction equation

HRID 1986086 reaction equation
[F:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[Si:11]([O:28][CH2:29][CH2:30][C:31]1[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=1[NH2:33])([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>S(Cl)(Cl)=O.C(Cl)Cl>[Si:11]([O:28][CH2:29][CH2:30][C:31]1[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=1[NH:33][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[N:10][C:2]=1[F:1])([C:24]([CH3:27])([CH3:25])[CH3:26])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 2

HCID 960892-Fluoronicotinic acidHCID 57721334HCID 57721334, compound

Product 1

HCID 57721337HCID 57721337, compoundYield 76.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A mixture of 2-fluoronicotinic acid (Aldrich, 0.42 g, 2.9 mmol) in thionyl chloride (15 mL) was refluxed for two hours before being concentrated in vacuo to a residue which was used without further purification. The residue was dissolved in anhydrous DCM (5 mL) then added dropwise to a 0° C. solution of 2-(2-(tert-butyldiphenylsilyloxy)ethyl)aniline (1.10 g, 2.9 mmol) and TEA (0.43 mL, 3.1 mmol) in anhydrous DCM (15 mL). The reaction was then stirred at ambient temperature for 16 hours before being quenched with water then stirred for an additional thirty minutes. The layers were separated and the aqueous layer extracted with DCM. The combined organic layers were washed sequentially with water, saturated aqueous NaHCO3, and brine before being dried over anhydrous MgSO4, and then concentrated in vacuo. The resultant residue was purified by silica gel flash chromatography, eluting with 4:1 hexane/EtOAc, to afford the desired compound as a white solid (1.1 g, 72%). 1H NMR (DMSO-d6) δ 9.93 (s, 1H), 8.41 (d, 1H, J=4.4 Hz), 8.22 (t, 1H, J=7.6 Hz), 7.27-7.60 (m, 15H), 3.84 (t, 2H, J=6.7 Hz), 2.98 (t, 2H, J=6.7 Hz), 0.92 (s, 9H); HRMS(ESI+), 499.2217 (M+H)+ calc, 499.2230 (M+H)+ found.

Workup

  1. temperaturewas refluxed for two hours
  2. concentrationbefore being concentrated in vacuo to a residue which
  3. customwas used without further purification
  4. dissolutionThe residue was dissolved in anhydrous DCM (5 mL)
  5. custombefore being quenched with water
  6. stirringthen stirred for an additional thirty minutes
  7. customThe layers were separated
  8. extractionthe aqueous layer extracted with DCM
  9. washThe combined organic layers were washed sequentially with water, saturated aqueous NaHCO3, and brine
  10. dry with materialbefore being dried over anhydrous MgSO4
  11. concentrationconcentrated in vacuo
  12. customThe resultant residue was purified by silica gel flash chromatography
  13. washeluting with 4:1 hexane/EtOAc

Sources & evidence

ORD record
ord-ba73c5755ba547838ba8a63861d27f78
Source dataset
uspto-grants-2009_06
Patent number
US07547782B2

Reaction notes

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