3-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2,6-dichloropyridine → 3-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-chloro-6-(2,6-difluorobenzyl)pyridine

HRID 1360704Notes

Reaction equation

HRID 1360704 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[C:11]([Cl:17])=[N:12][C:13](Cl)=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Br-].[F:19][C:20]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:21]=1[CH2:22][Zn+]>C1COCC1.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>[Si:1]([O:8][CH2:9][C:10]1[C:11]([Cl:17])=[N:12][C:13]([CH2:22][C:21]2[C:20]([F:19])=[CH:27][CH:26]=[CH:25][C:24]=2[F:28])=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 577003633-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2,6-dichloropyridineHCID 178505728HCID 178505728, compound

Product 1

HCID 577003793-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-chloro-6-(2,6-difluorobenzyl)pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,6-dichloropyridine (from Step B above, 8.5 g) in THF was added 2,6-difluorobenzylzinc bromide (90 mL, 0.5M in THF) and tetrakis(triphenylphosphine)palladium (2 g), and heated to reflux for a couple of hours until reaction completed. The mixture was cooled to room temperature and filtered through celite. The filtrate was diluted with ethyl acetate, washed with 1N NaOH, brine, dried over MgSO4 and concentrated to give title compound.

Workup

  1. temperatureheated
  2. temperatureto reflux for a couple of hours until reaction
  3. filtrationfiltered through celite
  4. additionThe filtrate was diluted with ethyl acetate
  5. washwashed with 1N NaOH, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-31a43381f5494887ad630097b615bf2e
Source dataset
uspto-grants-2011_02
Patent number
US07879875B2

Reaction notes

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