Diethyl Ether → HCID 178519029, compound

HRID 413237Notes

Reaction equation

HRID 413237 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.CCCCCC.CCOCC.I[C:23]1[CH:46]=[CH:45][C:26]2[NH:27][C:28]([N:30]3[CH2:35][CH2:34][C:33]4([C:43]5[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=5)[C:37](=[O:44])[O:36]4)[CH2:32][CH2:31]3)=[N:29][C:25]=2[CH:24]=1>C1COCC1.[Pd].CCOC(C)=O.[Cl-].[Zn+2].[Cl-].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:23]1[CH:46]=[CH:45][C:26]2[NH:27][C:28]([N:30]3[CH2:31][CH2:32][C:33]4([C:43]5[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=5)[C:37](=[O:44])[O:36]4)[CH2:34][CH2:35]3)=[N:29][C:25]=2[CH:24]=1

Participants

11

Reactant 5

HCID 3283Diethyl EtherHCID 8058Hexane2×HCID 9255OxazoleHCID 178418339Butyllithium2×HCID 1785190321'-(5-iodo-1H-benzimidazol-2-yl)spiro[isobenzofuran-1,4'-piperidin]-3-one

Product 1

HCID 178519029HCID 178519029, compound

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 3007855ZincchlorideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Add a solution of oxazole (0.5 mL, 7.24 mmol) in deoxygenated THF (50 mL) at −78° C. to 1.6 M n-butyllithium in hexane (5 mL, 7.96 mmol). After stirring for 30 minutes, add 1M zinc chloride in Et2O (22 mL, 21.7 mmol) and warm the reaction mixture to 0° C. for 2 hours. To the reaction mixture, add first a solution of 1′-(5-iodo-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one (3.2 g, 7.18 mmol), then the palladium catalyst which is prepared by treating a suspension of (Ph3P)2PdCl2 (0.25 g, 0.36 mmol) in deoxygenated THF (50 mL) with 1.6 M n-butyllithium in hexane (0.45 mL, 0.72 mmol). Reflux the reaction mixture for 20 hours. After cooling to ambient temperature, dilute the mixture with EtOAc (50 mL), and wash with water (50 mL) and saturated aqueous NaCl (50 mL). Dry the organic portion over Na2SO4, filter and concentrate. Purify by flash column chromatography (5% MeOH—CH2Cl2) to obtain 1′-(5-oxazol-2-yl-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4′-piperidin]-3-one as a white solid.

Workup

  1. additionby treating
  2. temperatureReflux the reaction mixture for 20 hours
  3. temperatureAfter cooling to ambient temperature
  4. washwash with water (50 mL) and saturated aqueous NaCl (50 mL)
  5. dry with materialDry the organic portion over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify by flash column chromatography (5% MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-27e3dafc44ed48a7a9e6d804e5533720
Source dataset
uspto-grants-2003_05
Patent number
US06566367B2

Reaction notes

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