Iodopyrazine → 4-(1-Phenyl-1-(pyrazin-2-yl)-methylene)-piperidine-1-carboxylic Acid tert-butyl Ester

HRID 606736Notes

Reaction equation

HRID 606736 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14](Br)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.I[C:28]1[CH:33]=[N:32][CH:31]=[CH:30][N:29]=1>C1COCC1.C(Cl)Cl.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:28]2[CH:33]=[N:32][CH:31]=[CH:30][N:29]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 642841IodopyrazineHCID 590345854-(1-Bromo-1-phenyl-methylene)-piperidine-1-carboxylic Acid tert-butyl EsterHCID 178418339Butyllithium

Product 1

HCID 670463344-(1-Phenyl-1-(pyrazin-2-yl)-methylene)-piperidine-1-carboxylic Acid tert-butyl EsterYield 68%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(1-bromo-1-phenyl-methylene)-piperidine-1-carboxylic acid tert-butyl ester (0.352 g, 1.0 mmol) in 4 mL of dry THF, at −78° C. under Ar, was added n-butyllithium solution (1.6M in hexanes, 0.75 mL, 1.2 mmol) dropwise. After 15 min, a solution of freshly fused ZnCl2 in 1.2 mL of dry THF was added dropwise and then the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. To this mixture was then added 2-iodopyrazine (0.119 mL, 1.2 mmol) and (Ph3P)4Pd (0.058 g, 5 mol %) and the reaction vessel was sealed and then heated at 90° C. for 16 h. The cooled mixture was quenched with saturated aqueous NH4Cl and then it was partitioned with EtOAc-water. The organic phase was washed (brine), dried (Na2SO4) and evaporated to give a dark brown gum. Flash chromatography of this material [SiO2/1-2% MeOH—NH4OH (9:1) in CH2Cl2] afforded the title compound (0.237 g, 68%) as a light yellow solid:

Workup

  1. customthe cooling bath was removed
  2. temperatureheated at 90° C. for 16 h
  3. customThe cooled mixture was quenched with saturated aqueous NH4Cl
  4. customit was partitioned with EtOAc-water
  5. washThe organic phase was washed (brine)
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customto give a dark brown gum

Sources & evidence

ORD record
ord-1069b061111246a595c2b721f67bb00e
Source dataset
uspto-grants-2011_03
Patent number
US07915283B2

Reaction notes

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