Cesium carbonate → 3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)aniline

HRID 1050153Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=2)[NH2:12])O1.Br[C:22]1[CH:23]=[N:24][N:25](C(OC(C)(C)C)=O)[CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH:24]1[CH:23]=[C:22]([C:9]2[CH:10]=[C:11]([CH:13]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:15]=2)[NH2:12])[CH:26]=[N:25]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)aniline (500 mg, 1.742 mmol) in 1,4-dioxane (12 mL) and water (3 mL) was added tert-butyl 4-bromo-1H-pyrazole-1-carboxylate (473 mg, 1.916 mmol), PdCl2(dppf) (127 mg, 0.174 mmol) and Cs2CO3 (1135 mg, 3.48 mmol). The mixture was stirred at 100° C. for 16 h under N2. The mixture was filtered and concentrated, which was purified by silica column chromatography (PE/EA=1:1). All fractions found to contain product by TLC (PE/EA=1:1, Rf=0.2) were combined and concentrated. Then the residue was purified by preparative TLC (DCM/MeOH=15:1, Rf=0.6) to yield a yellow solid of 3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)aniline (8 mg, 0.030 mmol, 1.7% yield): 1H NMR (400 MHz, CD3OD) δ 7.93 (s., 2H), 7.08 (s, 1H), 7.06 (s, 1H), 6.78 (s, 1H). ES-LCMS m/z 228.1 (M+H).

Workup

filtrationThe mixture was filtered
concentrationconcentrated
customwhich was purified by silica column chromatography (PE/EA=1:1)
concentrationconcentrated
customThen the residue was purified by preparative TLC (DCM/MeOH=15:1, Rf=0.6)

Sources & evidence

ORD record: ord-f509d3ab581e4386a8745d937addfed8
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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