Toluene → 4-Methyl-3-(5-methylpyridin-2-yl)aniline

HRID 1505042Notes

Reaction equation

HRID 1505042 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.Cl[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>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.CCO>[CH3:17][C:5]1[CH:4]=[CH:3][C:2]([NH2:1])=[CH:7][C:6]=1[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][N:20]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 5813932-Chloro-5-methyl-pyridineHCID 160860894-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 574932814-Methyl-3-(5-methylpyridin-2-yl)aniline

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a round-bottom flask containing 5-amino-2-methyl-phenylboronic acid pinacol ester (348 mg, 1.5 mmol), 2-chloro-5-methylpyridine (381 mg, 3 mmol), Pd(PPh3)4 (192 mg, 0.15 mmol) is added toluene (12 ml), EtOH (3 ml) and 2M aqueous Na2CO3 solution (3 ml). The flask is purged with argon and sealed. The mixture is stirred at 90° C. for 18 hours, cooled to room temperature and then water (20 ml) and ethyl acetate (20 ml) are added. The organic layer is separated, washed with brine, dried over MgSO4 and concentrated. The residue is purified by silica gel flash chromatography, eluted with 2% methanol in dichloromethane to afford 4-Methyl-3-(5-methylpyridin-2-yl)aniline as a brown oil. LC-MS m/z: 199.1 (M+1).

Workup

  1. customThe flask is purged with argon
  2. customsealed
  3. temperaturecooled to room temperature
  4. additionwater (20 ml) and ethyl acetate (20 ml) are added
  5. customThe organic layer is separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel flash chromatography
  10. washeluted with 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-152bcdb22cd045f197c7bb75dcecb770
Source dataset
uspto-grants-2015_12
Patent number
US09216964B2

Reaction notes

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