Triethylamine → HCID 71295154, compound

HRID 1776914Notes

Reaction equation

HRID 1776914 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].[NH2:8][C:9]1[C:29]([Br:30])=[CH:28][C:12]2[C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[O:15][C:11]=2[CH:10]=1.CCN(CC)CC.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CC#N.O>[Br:30][C:29]1[C:9]([N:8]2[CH2:2][CH2:3][CH2:4][C:5]2=[O:6])=[CH:10][C:11]2[O:15][C:14]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)=[C:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:12]=2[CH:28]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 783704-Chlorobutyryl chlorideHCID 67393744HCID 67393744, compound

Product 1

HCID 71295154HCID 71295154, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

4-chlorobutanoyl chloride (670 mg, 4.76 mmol) was added dropwise to a 0° C. solution of ethyl 6-amino-5-bromo-2-(4-fluorophenyl)benzofuran-3-carboxylate and Et3N (1.0 mL) in CH2Cl2 (10 mL) under N2 atmosphere. The resulting reaction was allowed to stir at room temperature for 16 hours, then the reaction mixture was concentrated in vacuo. The resulting resulting residue was dissolved in CH3CN (10 mL), and then K2CO3 (658 mg, 4.76 mmol) and KI (263 mg, 1.59 mmol) was added and the mixture was heated to reflux and allowed to stir at this temperature for 16 hours. After being cooled to room temperature, the mixture was diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue obtained was purified using column chromatography (eluted with petroleum ether:EtOAc=2:1) to provide ethyl 5-bromo-2-(4-fluorophenyl)-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxylate (280 mg, yield: 40%). 1H-NMR (CDCl3, 400 MHz) δ 8.32 (s, 1H), 8.04˜8.07 (m, 2H), 7.48 (s, 1H), 7.17˜7.21 (m, 2H), 4.42˜4.43 (m, 2H), 3.82˜3.86 (m, 2H), 2.61˜2.65 (m, 2H), 2.27˜2.31 (m, 2H), 1.40˜1.44 (m, 3H). MS (M+H)+: 446/448.

Workup

  1. customThe resulting reaction
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customThe resulting resulting residue
  4. temperaturethe mixture was heated
  5. temperatureto reflux
  6. stirringto stir at this temperature for 16 hours
  7. temperatureAfter being cooled to room temperature
  8. extractionextracted with EtOAc
  9. extractionThe organic extract
  10. washwas washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue obtained
  15. customwas purified
  16. washcolumn chromatography (eluted with petroleum ether:EtOAc=2:1)

Sources & evidence

ORD record
ord-c83b6f1ceba94e4ead8052247bb8bc8c
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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