Cesium carbonate → 6-(4-Bromo-3-formyl-phenoxy)-pyridine-2,3-dicarboxylic acid dimethyl ester

HRID 1483660Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][CH:8]=[C:7](Cl)[N:6]=1)=[O:4].[Br:16][C:17]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][C:18]=1[CH:19]=[O:20].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][CH:8]=[C:7]([O:25][C:22]2[CH:23]=[CH:24][C:17]([Br:16])=[C:18]([CH:19]=[O:20])[CH:21]=2)[N:6]=1)=[O:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-chloro-pyridine-2,3-dicarboxylic acid dimethyl ester (18, 4.0 g, 17.42 mmols) and 2-bromo-5-hydroxy-benzaldehyde (3.5 g, 17.42 mmol) in DMF (30 mL) was added cesium carbonate (11.35 g, 34.84 mmols). The resulting mixture was heated at 80° C. overnight. DMF was removed under reduced pressure, diluted with EtOAc (100 mL), washed with water (2×25 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 19 (1.14 g, 15%) as a light yellow oil. 1H NMR 400 MHz (DMSO-d6) δ: 10.18 (s, 1H), 8.38 (d, J=8.6 Hz, 1H), 7.90 (d, J=8.5 Hz, 1H), 7.66 (s, 1H), 7.55-7.52 (m, 1H), 7.36 (d, J=8.6 Hz, 1H), 3.86 (s, 3H), 3.84 (s, 3H); MS (ES) m/z: 394 (M+1)+, 396 (M+3)+.

Workup

customDMF was removed under reduced pressure
additiondiluted with EtOAc (100 mL)
washwashed with water (2×25 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-872394c2c5984e299d21bedbb570359d
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416146B2

Reaction notes

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