Sulfuric Acid → HCID 67513132, compound

HRID 1508526Notes

Reaction equation

HRID 1508526 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:8]=[C:9]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:10]=[N:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([F:21])[CH:14]=1.[I:27]N1C(=O)CCC1=O.C([O-])(O)=O.[Na+]>C(O)(=O)C>[Cl:6][C:7]1[CH:8]=[C:9]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:10]=[N:11][C:12]=1[C:13]1[CH:18]=[C:17]([I:27])[C:16]([O:19][CH3:20])=[C:15]([F:21])[CH:14]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 120273N-IodosuccinimideHCID 516892Sodium BicarbonateHCID 67513659HCID 67513659, compound

Product 1

HCID 67513132HCID 67513132, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Sulfuric acid (2.5 mL) was added into a cold (ice bath) mixture of ethyl 5-chloro-6-(3-fluoro-4-methoxyphenyl)pyridine-3-carboxylate (500 mg, 1.614 mmol) and 1-iodopyrrolidine-2,5-dione (400 mg, 1.776 mmol) in acetic acid (7.5 mL). The reaction mixture was stirred in an ice bath and warmed up to room temperature in one hour before placed in a 55° C. oil bath overnight. The crude was combined with the crude from an identical probe reaction (33 mg scale). The combined crude was poured into an ice/water mixture and neutralized by NaHCO3. The resulting mixture was extracted with EtOAc. The separated organic phase was dried over Na2SO4, filtered and evaporated to afford a dark mixture. This dark crude mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge). The column was eluted by an EtOAc/hexanes mixture (0% to 30%). Related fractions were pooled and evaporated to afford a white solid as the titled compound. LCMS calc.=434.95. found=435.77 (M+H)+. 1H NMR (CDCl3, 500 MHz) δ 9.13 (d, J=2.0 Hz, 1H), 8.38 (d, J=1.5 Hz, 1H), 8.02 (s, 1H), 7.60 (dd, J=12.5, 2.0 Hz, 1H), 4.45 (q, J=7.0 Hz, 2H), 4.03 (s, 3H), 1.44 (t, J=7.0 Hz, 3H).

Workup

  1. custombefore placed in a 55° C.
  2. customovernight
  3. customThe crude was combined with the crude from an identical probe reaction (33 mg scale)
  4. extractionThe resulting mixture was extracted with EtOAc
  5. dry with materialThe separated organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto afford a dark mixture
  9. customThis dark crude mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge)
  10. washThe column was eluted by an EtOAc/hexanes mixture (0% to 30%)
  11. customevaporated

Sources & evidence

ORD record
ord-1e6c48c8ec2447eaa07b5204fb8395f8
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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