Potassium Iodide → HCID 68575805, compound

HRID 272969Notes

Reaction equation

HRID 272969 reaction equation
[H-].[Na+].[CH:3]1([N:7]2[CH2:12][CH2:11][CH:10]([O:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:16][CH:15]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.Br[CH2:27][CH2:28][O:29][CH2:30][CH2:31]Br.[I-].[K+]>C1COCC1.CN1CCCC1=O>[CH:3]1([N:7]2[CH2:12][CH2:11][CH:10]([O:13][C:14]3[CH:15]=[CH:16][C:17]([C:20]4([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[CH:18][CH:19]=3)[CH2:9][CH2:8]2)[CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 21521Bis(2-bromoethyl) etherHCID 24758Sodium hydrideHCID 86601903HCID 86601903, compound

Product 1

HCID 68575805HCID 68575805, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

NaH (60% dispersion in oil, 800 mg, 20 mmol) was added at 0° C. to a solution of ethyl {4-[(1-cyclobutylpiperidin-4-yl)oxy]phenyl}acetate (2 g, 6.3 mmol) in THF (25 ml) and N-methylpyrrolidinone (2 ml) under nitrogen. The reaction was stirred at 0° C. for 15 minutes. Bis(2-bromoethyl)ether (1.2 ml, 9.54 mmol) and potassium iodide (500 mg, 3 mmol) were added and the mixture stirred at 0° C. for 45 minutes. The reaction was then warmed to room temperature and stirred for 18 hours. The reaction was cooled to 0° C., quenched with ice and solid carbon dioxide. The mixture was diluted with water and extracted with ethyl acetate (100 ml and 20 ml). The combined organic extracts were dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with ethyl acetate:diethylamine (99:1 by volume) to provide the title compound (870 mg, 36%) as a pale yellow oil. LRMS APCI+ m/z 388 [MH]+.

Workup

  1. stirringthe mixture stirred at 0° C. for 45 minutes
  2. temperatureThe reaction was then warmed to room temperature
  3. stirringstirred for 18 hours
  4. temperatureThe reaction was cooled to 0° C.
  5. customquenched with ice and solid carbon dioxide
  6. additionThe mixture was diluted with water
  7. extractionextracted with ethyl acetate (100 ml and 20 ml)
  8. dry with materialThe combined organic extracts were dried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by flash chromatography on silica gel eluting with ethyl acetate:diethylamine (99:1 by volume)

Sources & evidence

ORD record
ord-38912184424f4cffbac83003eda3abb7
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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