Ammonium Hydroxide → HCID 59594021, compound

HRID 1910356Notes

Reaction equation

HRID 1910356 reaction equation
[Cu]C#N.[C:4]([Mg]Cl)([CH3:7])([CH3:6])[CH3:5].[C:10]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:15]=[CH:14][CH:13]=[C:12]([C:16]2[CH:21]=[CH:20][C:19](Br)=[CH:18][N:17]=2)[CH:11]=1.[OH-].[NH4+]>C1COCC1>[C:10]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:15]=[CH:14][CH:13]=[C:12]([C:16]2[CH:21]=[CH:20][C:19]([C:4]([CH3:7])([CH3:6])[CH3:5])=[CH:18][N:17]=2)[CH:11]=1

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 67424558HCID 67424558, compoundHCID 178418310HCID 178418310, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 59594021HCID 59594021, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of copper(I) cyanide (17.3 g, 11 mmol) in 1730 mL of anhydrous THF in an oven-dried, five liter, three-necked flask equipped with a mechanical stirrer and a nitrogen inlet was added tert-butylmagnesium chloride (200 mL, 2.0 M, 400 mmol) via an addition funnel, and the mixture was stirred at −78° C. for 30 min. A solution of 2-(biphenyl-3-yl)-5-bromopyridine (15.0 g, 48 mmol) in 100 mL of dry THF was then added dropwise, and the mixture was stirred for 3 hours at −78° C. and then overnight at room temperature. Saturated aqueous ammonium hydroxide was then added to quench the reaction mixture, the pH was adjusted to 10 with aqueous sodium hydroxide, and the mixture was extracted with methylene chloride. The organic layer was dried over magnesium sulfate and evaporated to dryness to give 9.0 g of light yellow liquid that was purified by flash silica gel chromatography with a 2.5/97.5 to 7.5/92.5 ethyl acetate/hexane gradient as the eluent, affording 2.6 g (19%) of 2-(biphenyl-3-yl)-5-tert-butylpyridine as a colorless liquid.

Workup

  1. customequipped with a mechanical stirrer and a nitrogen inlet
  2. stirringthe mixture was stirred for 3 hours at −78° C.
  3. customovernight
  4. customat room temperature
  5. customto quench the reaction mixture
  6. extractionthe mixture was extracted with methylene chloride
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customevaporated to dryness
  9. customto give 9.0 g of light yellow liquid that
  10. customwas purified by flash silica gel chromatography with a 2.5/97.5 to 7.5/92.5 ethyl acetate/hexane gradient as the eluent

Sources & evidence

ORD record
ord-a3f1aeb9ee99433da94a5fde5802a00b
Source dataset
uspto-grants-2013_12
Patent number
US08603645B2

Reaction notes

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