Cesium carbonate → 3-Bromo-6-(4-bromo-3-formyl-phenoxy)-pyridine-2-carboxylic acid ethyl ester

HRID 1483662Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:11]([Br:12])=[CH:10][CH:9]=[C:8](Cl)[N:7]=1)=[O:5])[CH3:2].[Br:14][C:15]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:16]=1[CH:17]=[O:18].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:11]([Br:12])=[CH:10][CH:9]=[C:8]([O:23][C:20]2[CH:21]=[CH:22][C:15]([Br:14])=[C:16]([CH:17]=[O:18])[CH:19]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 3-bromo-6-chloro-pyridine-2-carboxylic acid ethyl ester (22, 8.0 g, 30.24 mmol) and 2-bromo-5-hydroxy-benzaldehyde (7.29 g, 36.29 mmol) in DMF (100 mL) was added cesium carbonate (22.6 g, 69.55 mmol). The resulting mixture was heated at 80° C. overnight. DMF was removed under reduced pressure, and the residue was diluted with EtOAc (200 mL), washed with water (2×50 mL) and brine (50 mL) solution. The combined organic layers were dried over Na2SO4, filtered, and concentrated to give crude product which was purified by column chromatography (Silica gel 20% EtOAc in hexane) to yield title compound 23 (4.0 g, 31%) as transparent oil. 1H NMR 400 MHz (DMSO-d6) δ: 10.18 (s, 1H), 8.27 (d, J=8.6 Hz, 1H), 7.87 (d, J=7.6 Hz, 1H), 7.65 (s, 1H), 7.51 (dd, J=8.7, 2.9 Hz, 1H), 7.26 (d, J=8.9 Hz, 1H), 4.29 (q, J=7.1 Hz, 2H), 1.25 (t, J=7.0 Hz, 3H); MS (ES) m/z: 430 (M+1)+.

Workup

customDMF was removed under reduced pressure
additionthe residue was diluted with EtOAc (200 mL)
washwashed with water (2×50 mL) and brine (50 mL) solution
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto give crude product which
customwas purified by column chromatography (Silica gel 20% EtOAc in hexane)

Sources & evidence

ORD record: ord-6eaf0f16e627477388a18baf5ab0d326
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416146B2

Reaction notes

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