Iodine → HCID 67367347, compound

HRID 1500319Notes

Reaction equation

HRID 1500319 reaction equation
II.[Mg].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

A little iodine was added to a mixture of 31.2 g (5 eq) magnesium and 100 ml dry THF, followed over a period of 10 min by 10 g (0.25 eq) bromobenzene, and the mixture was stirred for a further 10 min. Once the reaction had started, 194.2 g (4.75 eq) bromobenzene dissolved in 500 ml THF were added dropwise over a period of 2 h and the mixture was stirred for a further 15 min. 70 g (1 eq) 1-benzyl-4-(pyrrolidin-1-yl)piperidine-4-carbonitrile dissolved in 450 ml THF were added over a period of 2 h to the Grignard reagent prepared in the preceding step and the mixture was then heated for 12 h at 80° C. The reaction course was monitored by thin-layer chromatography (10% MeOH/CHCl3). Once the conversion was complete, the reaction solution was cooled to 0° C., mixed with saturated NH4Cl solution, extracted with ethyl acetate (3×200 ml) and the combined organic phases were dried with Na2SO4. Following removal of the solvent under reduced pressure, 33 g (40%) of crude product were obtained in the form of an oil.

Workup

  1. additionwere added dropwise over a period of 2 h
  2. stirringthe mixture was stirred for a further 15 min
  3. customprepared in the preceding step
  4. temperaturethe reaction solution was cooled to 0° C.
  5. extractionextracted with ethyl acetate (3×200 ml)
  6. dry with materialthe combined organic phases were dried with Na2SO4
  7. customremoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-d38acd00d9de425fa2667f903a8e5728
Source dataset
uspto-grants-2015_12
Patent number
US09206156B2

Reaction notes

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