2,6-Dibromopyridine → 6-bromo-N-(3-fluorobenzyl)pyridin-2-amine

HRID 1963805Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.[F:9][C:10]1[CH:11]=[C:12]([CH2:16][NH2:17])[CH:13]=[CH:14][CH:15]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOC(C)=O>[Br:8][C:4]1[N:3]=[C:2]([NH:17][CH2:16][C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([F:9])[CH:11]=2)[CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 117.5 °C

Procedure

A solution of 2,6-dibromopyridine (7.1 g, 30.0 mmol) in NMP (16 mL) was mixed with a mixture of (3-fluorophenyl)methanamine (4.13 g, 33.0 mmol) and Huenig's Base (5.76 mL, 33.0 mmol). The resulting mixture was stirred under argon at 115-120° C. for about 168 hr. The mixture was then cooled to ambient temperature and diluted with EtOAc (250 mL). The organic layer was separated, washed with saturated aqueous sodium bicarbonate (2×), water (2×), brine (1×), dried over sodium sulfate, filtered, and concentrated in vacuo to yield a crude material. The crude material was purified by column chromatography [SiO2, 120 g, EtOAc/hexane=0/100 to 20/80] providing 6-bromo-N-(3-fluorobenzyl)pyridin-2-amine (7.11 g) as an off-white solid. LCMS (m/z): 281.1/283.1[M+H]+; Retention time=1.03 min.

Workup

temperatureThe mixture was then cooled to ambient temperature
customThe organic layer was separated
washwashed with saturated aqueous sodium bicarbonate (2×), water (2×), brine (1×)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customto yield a crude material
customThe crude material was purified by column chromatography [SiO2, 120 g, EtOAc/hexane=0/100 to 20/80]

Sources & evidence

ORD record: ord-ba8d622638464e03be5e418d9eca6aa6
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415381B2

Reaction notes

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