Toluene → HCID 86751474, compound

HRID 1490316Notes

Reaction equation

HRID 1490316 reaction equation
[Cl:1][C:2]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH:12][C:11]2[C:3]=1[N:4]=[C:5]1[C:10]=2[C:9]([F:19])=[CH:8][CH:7]=[CH:6]1.[C:20]1(C)C=CC=CC=1.O(C)S(C(F)(F)F)(=O)=O>C(OCC)C>[ClH:1].[Cl:1][C:2]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH+:12]([CH3:20])[C:11]2[C:3]=1[N:4]=[C:5]1[C:10]=2[C:9]([F:19])=[CH:8][CH:7]=[CH:6]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 9526Methyl triflateHCID 178505542HCID 178505542, compound

Product 1

HCID 86751474HCID 86751474, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 11-chloro-6-fluoroquindoline from Example 89 (0.110 g, 3.89 mmol) and toluene (5 ml, freshly distilled) stirring under nitrogen was added methyl triflate (0.110 mL, 0.972 mmol). The mixture stirred for 24 h at room temperature and was diluted with diethyl ether (15 mL) and filtered. The orange filter cake was placed under high vacuum for 24 h. The orange residue was suspended in chloroform (400 mL), 5% KOH (150 mL) was added, and the resulting violet organic solution was separated. The violet organic solution was dried (Na2SO4) and filtered. The violet filtrate was acidified with ethereal 1M HCl to a bright yellow endpoint and adsorbed onto basic alumina. The adsorbent was chromatographed over basic alumina (eluting with chloroform-ethyl acetate gradient from 1:0 to 4:1 until the eluent was free of impurities by TLC then eluting with 2% methanol in chloroform). The violet fractions were collected and concentrated to a small volume (20 mL). The violet solution was acidified with ethereal 1M HCl to a bright yellow endpoint. The mixture was cooled below room temperature and filtered. The filter cake rinsed with diethyl ether (5 mL) and dried under high vacuum at 45° C. for several days to yield 0.109 g (98%) of the title compound as a bright orange solid. The title compound is poorly soluble in all common NMR solvents; 1H NMR (DMSO-d6 /CD3OD 1:1 v/v) δ 8.64 (d, J=9.2, 1H), 8.63 (dd, J=8.0, J=1.2, 1H), 8.18 (ddd, J=9.2, J=6.6, J=1.2, 1H), 8.00 (ddd, J=8.4, J=6.2, J=1.2, 1H), 7.87 (td, J=8.4, J=5.2, 1H), 7.59 (dd, J=8.4, J=0.4, 1H), 7.22 (ddd, J=13.6, J=8.0, J=0.8, 1H), 4.98 (s, 3H).

Workup

  1. stirringThe mixture stirred for 24 h at room temperature
  2. filtrationfiltered
  3. addition5% KOH (150 mL) was added
  4. customthe resulting violet organic solution was separated
  5. dry with materialThe violet organic solution was dried (Na2SO4)
  6. filtrationfiltered
  7. customThe adsorbent was chromatographed over basic alumina (
  8. washeluting with chloroform-ethyl acetate gradient from 1:0 to 4:1 until the eluent
  9. washthen eluting with 2% methanol in chloroform)
  10. customThe violet fractions were collected
  11. concentrationconcentrated to a small volume (20 mL)
  12. temperatureThe mixture was cooled below room temperature
  13. filtrationfiltered
  14. washThe filter cake rinsed with diethyl ether (5 mL)
  15. customdried under high vacuum at 45° C. for several days

Sources & evidence

ORD record
ord-8325ed0876d2439998f0b127c943f62d
Source dataset
uspto-grants-1997_10
Patent number
US05681958

Reaction notes

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