4-Fluoro-N-methylaniline → N-(4-fluorophenyl)-6-methoxy-N-methylpyridin-3-amine

HRID 1948264

Reaction equation

HRID 1948264 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CC([O-])(C)C.[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[F:62][C:63]1[CH:68]=[CH:67][C:66]([NH:69][CH3:70])=[CH:65][CH:64]=1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:62][C:63]1[CH:68]=[CH:67][C:66]([N:69]([CH3:70])[C:2]2[CH:7]=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)=[CH:65][CH:64]=1

Participants

7

Reactant 4

HCID 680244-Fluoro-N-methylanilineHCID 634876Binap, (A+-)-HCID 27348955-Bromo-2-methoxypyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 69344815N-(4-fluorophenyl)-6-methoxy-N-methylpyridin-3-amineYield 8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

According to Scheme 22 Method B: To a mixture of 5-bromo-2-methoxypyridine (1 eq, 1.06 mmol, 0.14 mL), KOtBu (1.5 eq, 1.60 mmol, 0.18 g), Pd(OAc)2 (0.02 eq, 21 μmol, 48 mg), BINAP (0.04 eq, 42 μmol, 26 mg) in degassed DMF (1.5 mL) was added 4-fluoro-N-methylbenzenamine (1.2 eq, 1.28 mmol, 0.14 mL). The reaction mixture was microwaved at 130° C. for 5 min. The reaction mixture was quenched with water and the aqueous phase was extracted with AcOEt. The organic fraction washed brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (AIT Flashsmart prepacked column 15 g SiO2, CH2Cl2/AcOEt 90/10) to afford N-(4-fluorophenyl)-6-methoxy-N-methylpyridin-3-amine (0.08 mmol, 20 mg, 8%) as a yellow oil.

Workup

  1. customThe reaction mixture was microwaved at 130° C. for 5 min
  2. customThe reaction mixture was quenched with water
  3. extractionthe aqueous phase was extracted with AcOEt
  4. washThe organic fraction washed brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by silica gel chromatography (AIT Flashsmart prepacked column 15 g SiO2, CH2Cl2/AcOEt 90/10)

Sources & evidence

ORD record
ord-0ac0dac57ae7483bb5880c6c3bad3dc0
Source dataset
uspto-grants-2013_03
Patent number
US08399493B2

Linked notes

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