6-Bromo-3-fluoropyridine-2-carbaldehyde → HCID 86671309, compound

HRID 1472882Notes

Reaction equation

[F:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:15]1[N:20]=[C:19]([CH:21]=[O:22])[C:18]([F:23])=[CH:17][CH:16]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:23][C:18]1[CH:17]=[CH:16][C:15]([C:6]2[CH:7]=[N:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=2)=[N:20][C:19]=1[CH:21]=[O:22]

Participants

Conditions

Temperature: 80 °C

Procedure

Nitrogen was bubbled through a mixture of 6-(trifluoromethyl)pyridin-3-ylboronic acid (3.74 g, 19.61 mmol), 6-bromo-3-fluoropicolinaldehyde (4.0 g, 19.61 mmol), Pd(Ph3P)4 (0.340 g, 0.294 mmol) was added and nitrogen was bubbled for 10 minutes, and the reaction mixture was heated overnight at 80° C. EtOAc (300 mL) was added and the mixture was washed with water (300 mL) and brine (300 mL), dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on a Grace Reveleris 80 g column, eluted with 0-40% EtOAc in Heptane (30 mL/min) to provide the title compound (3.681 g, 13.62 mmol, 69.5% yield). MS (ESI+) m/z 303.0 (M+H+MeOH); 1H NMR (300 MHz, DMSO-d6) δ 10.15 (s, 1H), 9.50 (d, J=2.0, 1H), 8.82-8.75 (m, 1H), 8.58 (dd, J=8.9, 3.7, 1H), 8.23-8.13 (m, 1H), 8.10 (d, J=8.3, 1H).

Workup

additionwas added
customnitrogen was bubbled for 10 minutes
additionEtOAc (300 mL) was added
washthe mixture was washed with water (300 mL) and brine (300 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed on a Grace Reveleris 80 g column
washeluted with 0-40% EtOAc in Heptane (30 mL/min)

Sources & evidence

ORD record: ord-1814e1092c2b491a9a800b9399dce888
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012651B2

Reaction notes

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