Dimethylacetamide → Methyl 4-(3-cyanophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601844Notes

Reaction equation

HRID 601844 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]2[C:15]3[CH:14]=[C:13]([C:16]([O:18][CH3:19])=[O:17])[NH:12][C:11]=3[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C[C:21]([N:23](C)C)=O>O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([C:2]1[CH:3]=[C:4]([CH:8]2[C:15]3[CH:14]=[C:13]([C:16]([O:18][CH3:19])=[O:17])[NH:12][C:11]=3[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1)#[N:23]

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 59180243Methyl 4-(3-bromophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Product 1

HCID 59180053Methyl 4-(3-cyanophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

Methyl 4-(3-bromophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.103 g, 0.32 mmol) was combined with zinc cyanide (0.046 g, 0.39 mmol) and dissolved in dimethyl acetamide (3 mL). Then the solution was evacuated and back-flushed with N2 four times and sparged with N2 for an additional 5-10 min. Tetrakis(triphenylphosphine)palladium(0) (0.091 g, 0.08 mmol) was added and the reaction placed in a preheated (85° C.) heating block and stirred for 2 hour. The reaction was then cooled to room temperature and diluted with aqueous H2O (40 mL) and extracted three times with ethyl acetate. The organic layer was washed once with brine, then dried over Na2SO4. Purification by column chromatography (Isco CombiFlash) eluting with a gradient of 0-40% EtOAc/heptane afforded the title compound. 0.021 g. LCMS-MS (ESI+) 289.2 (M+Na).

Workup

  1. customThen the solution was evacuated
  2. customback-flushed with N2 four times
  3. customsparged with N2 for an additional 5-10 min
  4. customplaced in a preheated (85° C.)
  5. temperatureheating block
  6. extractionextracted three times with ethyl acetate
  7. washThe organic layer was washed once with brine
  8. dry with materialdried over Na2SO4
  9. customPurification by column chromatography (Isco CombiFlash)
  10. washeluting with a gradient of 0-40% EtOAc/heptane

Sources & evidence

ORD record
ord-2a4fc0b570b7464aa7fd8f347b9280da
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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