Potassium Carbonate → HCID 86692460, compound

HRID 1748559Notes

Reaction equation

HRID 1748559 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]#[N:12])[CH2:7][CH2:6]2)OCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br:23][C:24]1[CH:25]=[CH:26][C:27](F)=[N:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[Br:23][C:24]1[CH:25]=[CH:26][C:27]([C:8]2([C:11]#[N:12])[CH2:7][CH2:6][C:5](=[O:1])[CH2:10][CH2:9]2)=[N:28][CH:29]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27831685-Bromo-2-fluoropyridineHCID 111164331,4-Dioxaspiro[4.5]decane-8-carbonitrile

Product 1

HCID 86692460HCID 86692460, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To 1,4-dioxaspiro[4.5]decane-8-carbonitrile (13.4 g) described in Reference Example 82 (1) was added a 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (100 ml), stirred at 0° C., then a solution of 5-bromo-2-fluoropyridine (12.8 g) in tetrahydrofuran (20 ml) was added thereto, and stirred at room temperature for 1 hour. Tetrahydrofuran (20 ml) was added thereto, additionally stirred for 1 hour, then to the reaction solution was added an aqueous solution of potassium carbonate, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and then the solvent was evaporated in vacuo. To the residue were added water (10 ml) and trifluoroacetic acid (50 ml), and stirred at room temperature for 6 hours. The reaction solution was added to an aqueous solution of potassium carbonate, the mixture was extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give 1-(5-bromopyridin-2-yl)-4-oxocyclohexanecarbonitrile (13.08 g) as a pale yellow solid. MS (ESI) m/z: 279, 281 (M+H)+.

Workup

  1. stirringstirred at room temperature for 1 hour
  2. stirringadditionally stirred for 1 hour
  3. extractionextracted with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated in vacuo
  7. additionTo the residue were added water (10 ml) and trifluoroacetic acid (50 ml)
  8. stirringstirred at room temperature for 6 hours
  9. additionThe reaction solution was added to an aqueous solution of potassium carbonate
  10. extractionthe mixture was extracted with ethyl acetate
  11. washthe organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customthe solvent was evaporated in vacuo
  14. customThe residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-37ba6a365dc7407eb792c3911e8840b3
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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