4-(Trifluoromethyl)aniline → (6-Chloro-4-methyl-pyridin-2-yl)-(4-trifluoromethyl-phenyl)-amine

HRID 2427881Notes

Reaction equation

HRID 2427881 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.[F:10][C:11]([F:20])([F:19])[C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Cl:9][C:4]1[N:3]=[C:2]([NH:16][C:15]2[CH:17]=[CH:18][C:12]([C:11]([F:10])([F:19])[F:20])=[CH:13][CH:14]=2)[CH:7]=[C:6]([CH3:8])[CH:5]=1

Participants

7

Reactant 3

HCID 99644-(Trifluoromethyl)anilineHCID 111172342-Bromo-6-chloro-4-methylpyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 59161720(6-Chloro-4-methyl-pyridin-2-yl)-(4-trifluoromethyl-phenyl)-amineYield 56%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-bromo-6-chloro-4-methylpyridine (415 mg, 2.0 mmol) in toluene (10 mL) was added 4-trifluoromethylaniline (325 mg, 2.0 mL), Pd2(dba)3 (50 mg, XANTPHOS (50 mg), and t-BuOK (350 mg). The mixture was microwaved 30 minutes at 120° C., filtered through Celite and washed with CH2Cl2 (3×). The combined organic layers were concentrated. The residue was purified by chromatography on silica gel (20-40% CH2Cl2 heptane) to give the product as a white solid (320 mg, 56%). 1H NMR (300 MHz, CDCl3) δ 7.53-7.63 (m, 2H), 7.41-7.49 (m, 2H), 6.70 (s, 1H), 6.61 (s, 2H), 2.28 (s, 3H). MS m/e 287.1 (M+H)

Workup

  1. customThe mixture was microwaved 30 minutes at 120° C.
  2. filtrationfiltered through Celite
  3. washwashed with CH2Cl2 (3×)
  4. concentrationThe combined organic layers were concentrated
  5. customThe residue was purified by chromatography on silica gel (20-40% CH2Cl2 heptane)

Sources & evidence

ORD record
ord-bd681dc306864771836329bc8a576561
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

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