Methyl 1-methoxy-4-bromo-2-naphthoate → Methyl 4-[(6-chloropyridin-3-yl)methyl]-1-methoxy-2-naphthoate

HRID 335051Notes

Reaction equation

HRID 335051 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH3:13])=[C:4]([C:14]([O:16][CH3:17])=[O:15])[CH:3]=1.[Cl-].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][Zn+])=[CH:22][N:21]=1>C1COCC1.O.C(OCC)(=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>[Cl:19][C:20]1[N:21]=[CH:22][C:23]([CH2:26][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([O:12][CH3:13])=[C:4]([C:14]([O:16][CH3:17])=[O:15])[CH:3]=2)=[CH:24][CH:25]=1

Participants

7

Reactant 2

HCID 12084039Methyl 1-methoxy-4-bromo-2-naphthoateHCID 178478124HCID 178478124, compound

Product 1

HCID 86677537Methyl 4-[(6-chloropyridin-3-yl)methyl]-1-methoxy-2-naphthoate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 4-bromo-1-methoxy-2-naphthoate (see Example 2, 0.500 g, 1.69 mmol) in 5 mL of THF under an atmosphere of nitrogen was added (2-chloro-5-pyridyl)methylzinc chloride (0.5 M in THF, 10.2 mL, 5.08 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.050 g, 0.043 mmol). The reaction was heated at 90° C. for 2 hours, then cooled to room temperature and diluted with water and ethyl acetate. The mixture was filtered through celite and the organic solution was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-20% ethyl acetate in hexanes to provide methyl 4-[(6-chloropyridin-3-yl)methyl]-1-methoxy-2-naphthoate that gave a mass ion (ES+) of 342.0 for [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe mixture was filtered through celite
  3. washthe organic solution was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via silica gel chromatography
  8. washeluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f5382ea356e744ffb8e72d7975cfbcba
Source dataset
uspto-grants-2014_11
Patent number
US08883850B2

Reaction notes

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