2,2,6,6-Tetramethylpiperidine → 4-(5-Tributylstannanyl-pyrazol-1-yl)-benzonitrile

HRID 1497748Notes

Reaction equation

HRID 1497748 reaction equation
C([Li])CCCCC.CC1(C)CCCC(C)(C)N1.[N:18]1([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[CH:22]=[CH:21][CH:20]=[N:19]1.[CH2:31]([Sn:35](Cl)([CH2:40][CH2:41][CH2:42][CH3:43])[CH2:36][CH2:37][CH2:38][CH3:39])[CH2:32][CH2:33][CH3:34]>C1COCC1>[CH2:40]([Sn:35]([CH2:31][CH2:32][CH2:33][CH3:34])([CH2:36][CH2:37][CH2:38][CH3:39])[C:22]1[N:18]([C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=2)[N:19]=[CH:20][CH:21]=1)[CH2:41][CH2:42][CH3:43]

Participants

6

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 15096Tributyltin ChlorideHCID 120796294-(1-Pyrazolyl)benzonitrileHCID 178506865HCID 178506865, compound

Product 1

HCID 867080884-(5-Tributylstannanyl-pyrazol-1-yl)-benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

Hexyl lithium (2.3 M in hexanes) (16.96 mL, 39.01 mmol) was added to a stirred solution of 2,2,6,6-tetramethyl-piperidine (6.85 mL, 40.63 mmol) in dry THF (15 mL) at −30° C. and the resulting suspension was stirred for 20 minutes. The suspension was allowed to warm to 10° C. to aid dissolution and was added, via cannula, to a solution of 4-pyrazol-1-yl-benzonitrile (5.50 g, 32.51 mmol, prepared according to Bioorganic & Medicinal Chemistry Letters, 2006, 16(11), 2955-2959, which is incorporated herein by reference in its entirety) in THF (85 mL) at −78° C., keeping the internal reaction temperature<-50° C. The resulting reaction mixture was stirred at −75° C. for 4 hrs and tributyl tin(IV) chloride (9.08 mL, 33.49 mmol) was added keeping the internal reaction temperature<-60° C. during addition. The reaction mixture was stirred at −60° C. for 1.5 rsh then allowed to warm to RT. The resulting solution was quenched by addition of EtOAc (100 mL) and then washed with water (2×50 mL) followed by saturated brine (50 mL). The organic extract was dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was purified by flash chromatography, eluting with a gradient of 0-5% EtOAc in pentane to give the title compound as an amber oil that solidified on standing (10.11 g).

Workup

  1. dissolutiondissolution
  2. customprepared
  3. customat −78° C.
  4. customthe internal reaction temperature<-50° C
  5. customThe resulting reaction mixture
  6. stirringwas stirred at −75° C. for 4 hrs
  7. customthe internal reaction temperature<-60° C.
  8. additionduring addition
  9. stirringThe reaction mixture was stirred at −60° C. for 1.5 rsh
  10. temperatureto warm to RT
  11. customThe resulting solution was quenched by addition of EtOAc (100 mL)
  12. washwashed with water (2×50 mL)
  13. extractionThe organic extract
  14. dry with materialwas dried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe resultant residue was purified by flash chromatography
  18. washeluting with a gradient of 0-5% EtOAc in pentane

Sources & evidence

ORD record
ord-62d31bab2bcd4a558ad94ee6af54644b
Source dataset
uspto-grants-2015_12
Patent number
US09199984B2

Reaction notes

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