Iodine → HCID 67367347, compound

HRID 2387950Notes

Reaction equation

HRID 2387950 reaction equation
[Mg].II.Br[C:5]1[CH:10]=[CH:9]C=[CH:7][CH:6]=1.[CH2:11]([N:18]1[CH2:23][CH2:22][C:21]([N:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)([C:24]#N)[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH4+].[Cl-]>C1COCC1.CO.C(Cl)(Cl)Cl>[CH2:11]([N:18]1[CH2:23][CH2:22][C:21]([C:24]2[CH:9]=[CH:10][CH:5]=[CH:6][CH:7]=2)([N:26]2[CH2:27][CH2:28][CH2:29][CH2:30]2)[CH2:20][CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 5

HCID 807IodineHCID 7961Bromobenzene2×HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 25219319HCID 25219319, compound

Product 1

HCID 67367347HCID 67367347, compoundYield 161.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 31.2 g (5 equiv.) of magnesium and 100 ml of dry THF there were added first a small amount of iodine and then, over a period of 10 minutes, 10 g (0.25 equiv.) of bromobenzene, and stirring was carried out for a further 10 minutes. When the reaction had started, 194.2 g (4.75 equiv.) of bromobenzene dissolved in 500 ml of THF were added dropwise over a period of 2 hours, and stirring was then carried out for 15 minutes. 70 g (1 equiv.) of 1-benzyl-4-(pyrrolidin-1-yl)piperidine-4-carbonitrile dissolved in 450 ml of THF were added over a period of 2 hours to the Grignard reagent prepared above, and finally the mixture was heated for 12 hours at 80° C. The progress of the reaction was monitored by thin-layer chromatography (10% MeOH/CHCl3). When the reaction was complete, the reaction solution was cooled to 0° C., saturated NH4Cl solution was added, extraction with ethyl acetate (3×200 ml) was carried out, and the combined organic phases were dried with Na2SO4. After removal of the solvent under reduced pressure, 33 g (40%) of crude product were obtained in the form of an oil.

Workup

  1. waitwas carried out for a further 10 minutes
  2. additionwere added dropwise over a period of 2 hours
  3. waitwas then carried out for 15 minutes
  4. customprepared above, and finally the mixture
  5. temperaturethe reaction solution was cooled to 0° C.
  6. extractionextraction with ethyl acetate (3×200 ml)
  7. dry with materialthe combined organic phases were dried with Na2SO4
  8. customAfter removal of the solvent under reduced pressure

Sources & evidence

ORD record
ord-2a7b4010aa0d4f02965563fc569efcbe
Source dataset
uspto-grants-2012_09
Patent number
US08269000B2

Reaction notes

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