4-Bromoaniline → 4'-(Trifluoromethyl)[1,1'-biphenyl]-4-amine

HRID 1427447Notes

Reaction equation

Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:14]([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=2)=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-bromoaniline (20 g, 116 mmol), 4-(trifluoromethyl)phenylboronic acid (15 g, 79 mmol), potassium carbonate (36.3 g, 263 mmol), and palladium(II) acetate (946 mg, 4.21 mmol) in 1,2-dimethoxyethane (80 mL) and water (80 mL) was stirred at 30° C. overnight. The reaction was then heated to 50° C. for 7 hours. The reaction was filtered through Celite and extracted with ethyl acetate (3×200 mL). The combined organics were washed with water and brine, dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (0.5-1.7% petroleum ether/ethyl acetate) gave 4′-(trifluoromethyl) biphenyl-4-amine (10 g, 40%) as an off white solid. 1H NMR (400 MHz, (CD3)2SO, δ): 7.73-7.82 (m, 4H), 7.55 (dd, 2H), 6.72 (d, 2H), 5.47 (s, 2H). MS (M+1): 238.2.

Workup

filtrationThe reaction was filtered through Celite
extractionextracted with ethyl acetate (3×200 mL)
washThe combined organics were washed with water and brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by column chromatography (0.5-1.7% petroleum ether/ethyl acetate)

Sources & evidence

ORD record: ord-cedc49ae6a2349c19f5aefd5b1152ced
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933104B2

Reaction notes

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