p-Toluidine → HCID 11473837, compound

HRID 1813969Notes

Reaction equation

HRID 1813969 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([C:9]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=2[O:16][CH3:17])[N:3]=1.[CH3:18][C:19]1[CH:20]=[CH:21][C:22]([NH2:25])=[CH:23][CH:24]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCCC1>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=2[O:16][CH3:17])[N:3]=[C:2]([NH:25][C:22]2[CH:23]=[CH:24][C:19]([CH3:18])=[CH:20][CH:21]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 7813p-ToluidineHCID 634876Binap, (A+-)-HCID 22504971HCID 22504971, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 11473837HCID 11473837, compoundYield 21.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 2,4-dichloro-6-(5-chloro-2-methoxy-phenyl)-pyridine (25 mg, 0.087 mmol), p-tolylamine (10.2 mg, 0.1 mmol), sodium tert-butoxide (26 mg, 0.26 mmol), and tetrahydrofuran (15 ml), degassed with argon, was added palladium acetate (15 mg, 0.066 mmol) followed by 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (30 mg, 0.048 mmol). The mixture was stirred at 70° C. for 5 hours and filtered through a pad of celite under suction. The filtrate was concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography eluting with ethyl acetate-hexane (1:9) to provide the title compound (6.6 mg, 21% yield). 1H NMR (acetone-d6) δ 2.32 (s, 3H, CH3), 3.95 (s, 3H, CH3), 6.83-6.84 (m, 1H, Ar), 7.15 (d, 2H, J=8.2 Hz, Ar), 7.20 (d, 1H, J=8.9 Hz, Ar), 7.43 (dd, 1H, J=8.8 Hz, J=2.8 Hz, Ar), 7.46 (d, 1H, J=1.5 Hz, Ar), 7.57-7.60 (m, 2H, Ar), 8.10 (d, 1H, J=2.7 Hz, Ar), 8.43 (s, 1H, NH).

Workup

  1. customdegassed with argon
  2. filtrationfiltered through a pad of celite under suction
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by preparative thin layer chromatography
  5. washeluting with ethyl acetate-hexane (1:9)

Sources & evidence

ORD record
ord-fc75096738c04aed8f8a926cda163bff
Source dataset
uspto-grants-2005_04
Patent number
US06875781B2

Reaction notes

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