Iodine → HCID 57831240, compound

HRID 453894Notes

Reaction equation

HRID 453894 reaction equation
II.[Mg].Br[C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20](C#N)([N:23]([CH3:25])[CH3:24])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[NH4+].[Cl-]>C(OCC)C.C1COCC1>[C:10]([O:14][C:15]([N:17]1[CH2:18][CH2:19][C:20]([N:23]([CH3:25])[CH3:24])([C:5]2[S:6][CH:7]=[CH:8][CH:9]=2)[CH2:21][CH2:22]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

8

Reactant 5

HCID 807IodineHCID 138512-Bromothiophene2×HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 575047971,1-Dimethylethyl 4-cyano-4-(dimethylamino)-1-piperidinecarboxylate

Product 1

HCID 57831240HCID 57831240, compoundYield 64.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A little iodine was added to a mixture of 5.6 g (3 eq.) magnesium and 20 ml dry diethyl ether, followed over a period of 10 min by 5 g 2-bromothiophene, and the mixture was stirred for a further 10 min. Once the reaction had started, 33.5 g (2.6 eq.) 2-bromothiophene dissolved in 80 ml diethyl ether were added dropwise and the mixture was stirred for a period of 2 h at room temperature. The Grignard reagent prepared in the preceding step was added dropwise to a solution of 20 g (1 eq.) tert-butyloxycarbonyl-4-cyano-4-(dimethylamino)piperidine dissolved in 200 ml THF and stirred overnight at room temperature. Once the conversion was complete, the reaction solution was cooled to 0° C., mixed with saturated NH4Cl solution, extracted with ethyl acetate (3×100 ml) and the combined organic phases were dried with Na2SO4. Following removal of the solvent under reduced pressure, the residue was purified by column chromatography (alox neutral; 30% EtOAc/hexane). 6.1 g (25%) of product were obtained in the form of a white solid.

Workup

  1. additionwere added dropwise
  2. stirringthe mixture was stirred for a period of 2 h at room temperature
  3. stirringstirred overnight at room temperature
  4. extractionextracted with ethyl acetate (3×100 ml)
  5. dry with materialthe combined organic phases were dried with Na2SO4
  6. customremoval of the solvent under reduced pressure
  7. customthe residue was purified by column chromatography (alox neutral; 30% EtOAc/hexane)

Sources & evidence

ORD record
ord-ce605e55236c456488cfea70f48c0155
Source dataset
uspto-grants-2013_07
Patent number
US08492559B2

Reaction notes

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