Iodine → HCID 57831240, compound

HRID 2387954Notes

Reaction equation

HRID 2387954 reaction equation
[Mg].II.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.CCOC(C)=O.CCCCCC>[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

9

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 3

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 5.6 g (3 equiv.) of magnesium and 20 ml of dry diethyl ether there were added first a small amount of iodine and then, over a period of 10 minutes, 5 g of 2-bromothiophene, and stirring was carried out for a further 10 minutes. When the reaction had started, 33.5 g (2.6 equiv.) of 2-bromothiophene dissolved in 80 ml of diethyl ether were added dropwise, and stirring was carried out over a period of 2 hours at room temperature. The Grignard reagent prepared above was added dropwise to a solution of 20 g (1 equiv.) of tert-butyloxycarbonyl-4-cyano-4-(dimethylamino)piperidine dissolved in 200 ml of THF, and stirring was carried out overnight at room temperature. The progress of the reaction was monitored by thin-layer chromatography (50% EtOAc/hexane). When the reaction was complete, the reaction solution was cooled to 0° C., saturated NH4Cl solution was added, extraction with ethyl acetate (3×100 ml) was carried out, and the combined organic phases were dried with Na2SO4. After removal of the solvent under reduced pressure, purification was carried out 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. waitwas carried out for a further 10 minutes
  2. additionwere added dropwise
  3. waitwas carried out over a period of 2 hours at room temperature
  4. stirringstirring
  5. waitwas carried out overnight at room temperature
  6. extractionextraction with ethyl acetate (3×100 ml)
  7. dry with materialthe combined organic phases were dried with Na2SO4
  8. customAfter removal of the solvent
  9. customunder reduced pressure, purification

Sources & evidence

ORD record
ord-452a11b590b04cb8ae2b5d5ea5f51dcc
Source dataset
uspto-grants-2012_09
Patent number
US08269000B2

Reaction notes

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