Cesium carbonate → Methyl 3-azido-2-(4-(2-methoxyethoxy)phenyl)-6-(4-methoxyphenyl)isonicotinate

HRID 2410722Notes

Reaction equation

[N:1]([C:4]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)=[N:12][C:11]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7])=[N+:2]=[N-:3].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:35][O:36][CH2:37][CH2:38]Br>C(#N)C>[N:1]([C:4]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH2:38][CH2:37][O:36][CH3:35])=[CH:18][CH:19]=2)=[N:12][C:11]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7])=[N+:2]=[N-:3]

Participants

Conditions

Temperature: 75 °C

Procedure

A mixture of methyl 3-azido-2-(4-hydroxyphenyl)-6-(4-methoxyphenyl)isonicotinate (83 mg, 0.221 mmol), cesium carbonate (359 mg, 1.10 mmol), and 2-bromoethyl methyl ether (0.062 mL, 0.662 mmol) in acetonitrile (1 mL) was heated at 75° C. for 5 hr. The reaction was partitioned between EtOAc and water. The organic phase was separated and washed with brine, dried with sodium sulfate and the solvent removed. Radial silica gel chromatography (step gradient elution with hexane containing 0 to 30% EtOAc) afforded 42 mg of methyl 3-azido-2-(4-(2-methoxyethoxy)phenyl)-6-(4-methoxyphenyl)isonicotinate as an oil. MS (ESI) m/z 435.1 (M+H). 1H NMR (CDCl3) δ ppm 8.02 (2H, d, J=8.55 Hz), 7.93 (1H, s), 7.78-7.86 (2H, m), 7.05 (2H, d, J=8.85 Hz), 6.98 (2H, d, J=8.85 Hz), 4.16-4.24 (2H, m), 4.02 (3H, s), 3.85 (3H, s), 3.75-3.81 (2H, m), 3.47 (3H, s).

Workup

customThe reaction was partitioned between EtOAc and water
customThe organic phase was separated
washwashed with brine
dry with materialdried with sodium sulfate
customthe solvent removed
washRadial silica gel chromatography (step gradient elution with hexane containing 0 to 30% EtOAc)

Sources & evidence

ORD record: ord-d6a5519620c64a8cb6a12a1a8d5efa5f
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815840B2

Reaction notes

Loading…