Iodine → HCID 67127506, compound

HRID 2422398Notes

Reaction equation

HRID 2422398 reaction equation
II.[Mg].Br[C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.[N:10]1([C:14]2(C#N)[CH2:23][CH2:22][C:17]3([O:21][CH2:20][CH2:19][O:18]3)[CH2:16][CH2:15]2)[CH2:13][CH2:12][CH2:11]1>C(OCC)C.C1COCC1.CCOC(C)=O.CCCCCC>[S:6]1[CH:7]=[CH:8][CH:9]=[C:5]1[C:14]1([N:10]2[CH2:11][CH2:12][CH2:13]2)[CH2:23][CH2:22][C:17]2([O:18][CH2:19][CH2:20][O:21]2)[CH2:16][CH2:15]1

Participants

8

Reactant 4

HCID 807IodineHCID 138512-Bromothiophene2×HCID 5462224MagnesiumHCID 57475115HCID 57475115, compound

Product 1

HCID 67127506HCID 67127506, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

A catalytic amount of iodine was added to magnesium (5.1 g) in 50 ml diethyl ether. After 10 minutes a solution of 2-bromothiophene (5.7 g) in 10 ml THF was added to this reaction mixture. Once the Grignard reaction had started, 2-bromothiophene (15 ml) dissolved in 50 ml THF was added dropwise and on completion of the addition the mixture was stirred for two hours at room temperature. 8-Azetidin-1-yl-1,4-dioxaspiro[4,5]decane-8-carbonitrile (12 g) dissolved in 60 ml THF was added dropwise to this reaction mixture at 60-70° C. under a nitrogen atmosphere. Then the reaction mixture was stirred for 1 hour at room temperature and the reaction progress was monitored by thin-layer chromatography (50% EtOAc/hexane). Once the conversion was complete the reaction mixture was cooled to 0° C., quenched with saturated ammonium chloride solution (50 ml) and then extracted with ethyl acetate (2×100 ml). The combined organic phases were dried over Na2SO4. Following removal of the solvent under reduced pressure, the residue was purified by column chromatography (silica, 5-10% EtOAc/hexane). The desired product was obtained as a brown solid (10.2 g, 68%).

Workup

  1. customOnce the Grignard reaction
  2. additionwas added dropwise and on completion of the addition the mixture
  3. additionwas added dropwise to this reaction mixture at 60-70° C. under a nitrogen atmosphere
  4. stirringThen the reaction mixture was stirred for 1 hour at room temperature
  5. temperaturewas cooled to 0° C.
  6. customquenched with saturated ammonium chloride solution (50 ml)
  7. extractionextracted with ethyl acetate (2×100 ml)
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. customremoval of the solvent under reduced pressure
  10. customthe residue was purified by column chromatography (silica, 5-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-577f20d407d2488ba095ee037726676a
Source dataset
uspto-grants-2011_06
Patent number
US07960404B2

Reaction notes

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