2,6-Dimethoxypyridine → HCID 67046436, compound

HRID 1394423Notes

Reaction equation

HRID 1394423 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[N:4]=1.[Li]CCCC.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][C:26](=[C:29](Br)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>C1COCC1.[Br-].[Zn+2].[Br-].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:16]([O:20][C:21]([N:23]1[CH2:24][CH2:25][C:26](=[C:29]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:8]2[C:3]([O:2][CH3:1])=[N:4][C:5]([O:9][CH3:10])=[CH:6][CH:7]=2)[CH2:27][CH2:28]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 3

HCID 803782,6-DimethoxypyridineHCID 590345854-(1-Bromo-1-phenyl-methylene)-piperidine-1-carboxylic Acid tert-butyl EsterHCID 178418339Butyllithium

Product 1

HCID 67046436HCID 67046436, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

To a solution of 2,6-dimethoxypyridine (0.211 g, 1.51 mmol) in dry THF (7 mL) at −78° C. under Ar was added n-BuLi (1.53 M in hexanes, 1.18 mL, 1.81 mmol) dropwise. After the addition, the mixture was stirred at 10° C. for 30 minutes and then it was re-cooled to −78° C. To this mixture was added a solution of (previously fused in vacuo) zinc bromide (0.407 g, 1.81 mmol) in THF (2 mL) and the reaction mixture was allowed to warm to ambient temperature. The resulting mixture was cannulated into a flame-dried flask containing 4-(1-bromo-1-phenyl-methylene)-piperidine-1-carboxylic acid tert-butyl ester (0.532 g, 1.51 mmol) and Pd(PPh3)4 under Ar. The vessel was sealed and the mixture was heated at 90° C. (oil bath temperature) for 4 h. The cooled mixture was then quenched with saturated NH4Cl and extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was then purified by flash chromatography (SiO2/CH2Cl2-hexane, 7:3) to afford the title compound (0.295 g, 48%) as a yellow gum:

Workup

  1. additionAfter the addition
  2. temperatureit was re-cooled to −78° C
  3. additionTo this mixture was added a solution of (
  4. temperatureto warm to ambient temperature
  5. customThe resulting mixture was cannulated into a flame-dried flask
  6. customThe vessel was sealed
  7. temperaturethe mixture was heated at 90° C. (oil bath temperature) for 4 h
  8. customThe cooled mixture was then quenched with saturated NH4Cl
  9. extractionextracted with EtOAc
  10. dry with materialThe organic phase was dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated to dryness
  13. customThe residue was then purified by flash chromatography (SiO2/CH2Cl2-hexane, 7:3)

Sources & evidence

ORD record
ord-3166cb2324b64b03b555933be29f5e73
Source dataset
uspto-grants-2008_03
Patent number
US07348337B2

Reaction notes

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