P-Anisidine → 5-Bromo-N-(4-methoxyphenyl)pyridin-3-amine

HRID 2064488Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)C.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]>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([NH:17][C:14]2[CH:15]=[CH:16][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)[CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 3,5-dibromopyridine (1.5 g, 6.3 mmol), p-anisidine (0.94 g, 7.60 mmol), (R)-(+)-2,2′-bis(diphenyl-phosphino)-1,1′-binapthyl (0.16 g, 0.25 mmol) and sodium tert-butoxide (0.85 g, 8.86 mmol) in toluene (15 ml) is deoxygenated using argon before adding Pd2(dba)3 (0.116 g, 0.13 mmol) and heating the mixture at 70° C. for 16 hours. The mixture is diluted with diethyl ether, washed with brine, dried over Na2SO4 and concentrated. The residue is chromatographed on silicagel to afford the product; 1H NMR (400 MHz, CDCl3): δ 8.16 (d, J=2.42 Hz, 1H), 8.04 (d, J=1.82 Hz, 1H), 7.30 (m, 1H), 7.09 (m, 2H), 6.90 (m, 2H), 5.89 (s, 1H), 3.81 (s, 3H).

Workup

customis deoxygenated
washwashed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residue is chromatographed on silicagel
customto afford the product

Sources & evidence

ORD record: ord-253e2a5e657d489ebe9ea83777b65b1b
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288421B2

Reaction notes

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