Hydrochloric Acid → HCID 58452334, compound

HRID 70583

Reaction equation

HRID 70583 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH3:10])[CH:3]=1.C([Li])[CH2:12][CH2:13][CH3:14].[B:16](OC(C)C)([O:21]C(C)C)[O:17][CH:18](C)C.Cl.O1CCC[CH2:31]1>CCCCCC>[CH3:31][C:13]1([CH3:14])[CH2:12][O:21][B:16]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH3:10])[CH:3]=2)[O:17][CH2:18]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 21531Triisopropyl borateHCID 1442674-Bromo-2-methylbenzonitrileHCID 178418339Butyllithium

Product 1

HCID 58452334HCID 58452334, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 4-bromo-2-methylbenzonitrile (1.0 g) in tetrahydrofuran (16 mL) was cooled to an external temperature of −78° C. in a nitrogen atmosphere, and a solution of n-butyllithium in hexane (1.57 M, 3.5 mL) was added dropwise. After stirring at −78° C. for 40 minutes, triisopropyl borate (1.5 mL) was added dropwise and the mixture was stirred at room temperature for 1.5 hours. 1 M hydrochloric acid (10 mL) was added to the reaction solution, followed by extraction with diethyl ether. The organic layer was washed with water and brine, dried over sodium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was dissolved in toluene (4 mL) and tetrahydrofuran (3 mL), and 2,2-dimethyl-1,3-propanediol (531 mg) and anhydrous magnesium sulfate (catalytic amount) were added, after which the mixture was stirred at room temperature for five minutes. The insoluble matter in the reaction solution was filtered off, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:1→20:1) to give the title compound as a colorless solid (778 mg, 67%).

Workup

  1. stirringthe mixture was stirred at room temperature for 1.5 hours
  2. extractionfollowed by extraction with diethyl ether
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was then evaporated under reduced pressure
  7. dissolutionThe residue was dissolved in toluene (4 mL)
  8. additiontetrahydrofuran (3 mL), and 2,2-dimethyl-1,3-propanediol (531 mg) and anhydrous magnesium sulfate (catalytic amount) were added
  9. stirringafter which the mixture was stirred at room temperature for five minutes
  10. filtrationThe insoluble matter in the reaction solution was filtered off
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:1→20:1)

Sources & evidence

ORD record
ord-f36dc87aec0a48c4ada52f8430ba6537
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Linked notes

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