Toluene → 3-(3,5-Difluoropyridin-2-yl)-4-methylaniline

HRID 1505064Notes

Reaction equation

HRID 1505064 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.[CH3:10][C:11]1[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][C:12]=1B1OC(C)(C)C(C)(C)O1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>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.C(O)C>[F:8][C:7]1[C:2]([C:12]2[CH:13]=[C:14]([CH:16]=[CH:17][C:11]=2[CH3:10])[NH2:15])=[N:3][CH:4]=[C:5]([F:9])[CH:6]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 160860894-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 450795602-Chloro-3,5-difluoropyridine

Product 1

HCID 583179983-(3,5-Difluoropyridin-2-yl)-4-methylaniline

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask is added 2-chloro-3,5-difluoropyridine (1.5 g, 10 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (2.2 g, 10 mmol), Pd(PPh3)4 (300 mg, 0.26 mmol), toluene (60 mL), ethanol (20 mL) and 2M Na2CO3 (20 mL, 40 mmol). The reaction is stirred under reflux condition for 15 hours. After cooling, the reaction mixture is diluted with ethyl acetate, washed with brine and dried over Na2SO4. The organic phase is then dried by rotary evaporation. The crude product is purified by silica gel flash chromatography to afford 3-(3,5-difluoropyridin-2-yl)-4-methylaniline as a light brown solid. MS m/z 221.1 (M+1).

Workup

  1. temperatureunder reflux condition for 15 hours
  2. temperatureAfter cooling
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customThe organic phase is then dried by rotary evaporation
  6. customThe crude product is purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-c7270ad199344a06951242840664023b
Source dataset
uspto-grants-2015_12
Patent number
US09216964B2

Reaction notes

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