Potassium Iodide → 9-[8-(2,2,2-Trifluoroacetyl)-8-aza-bicyclo[3.2.1]oct-3-yl]-9H-xanthene-3-carbonitrile

HRID 733409Notes

Reaction equation

HRID 733409 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:6]([CH:16]3[CH2:22][CH:21]4[N:23]([C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH:18]([CH2:19][CH2:20]4)[CH2:17]3)[C:7]3[C:12]([O:13][C:14]=2[CH:15]=1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[Cu](C#N)[C:31]#[N:32].[I-].[K+]>CN(C=O)C>[F:27][C:25]([F:26])([F:28])[C:24]([N:23]1[CH:21]2[CH2:20][CH2:19][CH:18]1[CH2:17][CH:16]([CH:6]1[C:5]3[CH:4]=[CH:3][C:2]([C:31]#[N:32])=[CH:15][C:14]=3[O:13][C:12]3[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH2:22]2)=[O:29]

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 578392651-[3-(3-Bromo-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-2,2,2-trifluoroethanone2×HCID 178418260HCID 178418260, compound2×

Product 1

HCID 578392559-[8-(2,2,2-Trifluoroacetyl)-8-aza-bicyclo[3.2.1]oct-3-yl]-9H-xanthene-3-carbonitrileYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[3-(3-bromo-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-2,2,2-trifluoro-ethanone, 2j (1.8 g, 3.86 mmol) in DMF (40 mL) was added copper cyanide (0.69 g, 7.72 mmol) and potassium iodide (50 mg), and the mixture was heated to reflux for 18 h. More copper cyanide (0.43 g) was added, and the mixture was heated to reflux for 30 h. The mixture was filtered and poured in ice-water. The solid was separated via filtration, washed with water, and air-dried. The crude product was purified via flash column chromatography (eluent gradient: 5% to 30% ethyl acetate in heptane) to yield 0.956 g (60%) of title compound 9-[8-(2,2,2-trifluoroacetyl)-8-aza-bicyclo[3.2.1]oct-3-yl]-9H-xanthene-3-carbonitrile, 3j. MS m/z (MH+) 412.8.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 18 h
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 30 h
  5. filtrationThe mixture was filtered
  6. additionpoured in ice-water
  7. customThe solid was separated via filtration
  8. washwashed with water
  9. customair-dried
  10. customThe crude product was purified via flash column chromatography (eluent gradient: 5% to 30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-86cce731f2f14898ae6c4fbfc5930a8a
Source dataset
uspto-grants-2009_09
Patent number
US07589104B2

Reaction notes

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