Diethyl Ether → 4-(Tert-butyl)-2-(5,6-dichloropyridin-3-yl)phenol

HRID 1480619Notes

Reaction equation

HRID 1480619 reaction equation
[C:1]([C:5]1[CH:6]=[CH:7][C:8]([O:14]COCCOC)=[C:9](B(O)O)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:22]1[CH:23]=[C:24]([Cl:29])[C:25]([Cl:28])=[N:26][CH:27]=1.C(=O)([O-])[O-].[K+].[K+].CCOCC>COCCOC.O.Cl.C(O)C.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]([C:5]1[CH:6]=[CH:7][C:8]([OH:14])=[C:9]([C:22]2[CH:27]=[N:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 127477605-Bromo-2,3-dichloropyridineHCID 86718562(5-(Tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)boronic acid2×

Product 1

HCID 901229404-(Tert-butyl)-2-(5,6-dichloropyridin-3-yl)phenol

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-(tert-butyl)-2-((2-methoxyethoxy)methoxy)benzeneboronic acid (Intermediate 7) (1.0 g, 3.54 mmol), 5-bromo-2,3-dichloropyridine (0.80 g, 3.53 mmol) and potassium carbonate (1.5 g, 10.85 mmol) in DME (20 mL) and water (5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium (0) (200.0 mg, 0.17 mmol) was added and the mixture heated at 80° C. overnight. The cooled reaction mixture was extracted with ethyl acetate (50 mL), the organic phase separated, dried (MgSO4), filtered and concentrated under reduced pressure. The product was purified using flash chromatography on silica eluting with 30% ethyl acetate in hexanes to give the MEM ether intermediate. The MEM ether was stirred in 10% hydrochloric acid in ethanol at room temperature for 4 hours. The reaction mixture was then concentrated under reduced pressure to give 4-(tert-butyl)-2-(5,6-dichloropyridin-3-yl)phenol.

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. customThe cooled reaction mixture
  3. extractionwas extracted with ethyl acetate (50 mL)
  4. customthe organic phase separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified
  9. customto give the MEM ether intermediate
  10. concentrationThe reaction mixture was then concentrated under reduced pressure

Sources & evidence

ORD record
ord-9e51096da5d54d32a11f1c3c512e2d75
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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