Chlorotrimethylsilane → Ethyl (quinolin-2-yl)acetate

HRID 920887Notes

Reaction equation

HRID 920887 reaction equation
C[Si](Cl)(C)C.Br[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].Br[C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1.C(OCC)(=O)C>C1COCC1.[Zn].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH2:11]([O:10][C:8](=[O:9])[CH2:7][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1)[CH3:12]

Participants

9

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7748Ethyl bromoacetateHCID 8857Ethyl AcetateHCID 27627562-Bromoquinoline

Product 1

HCID 12481727Ethyl (quinolin-2-yl)acetateYield 48.4%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a suspension of vacuum dried Zn dust (6.0 g, 93.8 mmol) in dry THF (100 mL) was added TMSCl (0.5 mL) dropwise over 5 min under N2 atmosphere and under stirring. The mixture was stirred for 30 min and warmed to 45° C. Ethyl bromoacetate (5.2 mL, 46.9 mmol) was added dropwise via a syringe. After addition, the mixture was stirred at the same temperature for 1 h. After sedation at room temperature for 2 h, a clear orange solution was formed. The orange solution (50 mL) was carefully sucked into a syringe through a long needle and added to a mixture of 2-bromoquinoline (2.0 g, 9.6 mmol) and PdCl2(dppf) (200 mg, 0.27 mmol) in a three-neck flask. The mixture was refluxed under N2 for 3 h. The reaction was monitored with LC-MS. Ethyl acetate (200 mL) was added to dilute the mixture and water (50 mL) was added to quench the reaction. The mixture was filtered through a celite pad. The filtration was partitioned between brine and ethyl acetate. The organic layer was separated, washed with brine (100 mL), dried over sodium sulfate and concentrated. The residue was purified with silica column (PE/EA=3:1) to give the title compound as orange oil (1.0 g, 48%). LC-MS (ESI+): m/e 216 (M+H)+, Rt: 0.62 min.

Workup

  1. stirringThe mixture was stirred for 30 min
  2. additionAfter addition
  3. stirringthe mixture was stirred at the same temperature for 1 h
  4. customa clear orange solution was formed
  5. temperatureThe mixture was refluxed under N2 for 3 h
  6. additionwas added
  7. customto quench
  8. customthe reaction
  9. filtrationThe mixture was filtered through a celite pad
  10. filtrationThe filtration
  11. customwas partitioned between brine and ethyl acetate
  12. customThe organic layer was separated
  13. washwashed with brine (100 mL)
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. customThe residue was purified with silica column (PE/EA=3:1)

Sources & evidence

ORD record
ord-c2c365fc18fd40069409ade865717d3a
Source dataset
uspto-grants-2016_03
Patent number
US09273068B2

Reaction notes

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