4-Bromophenol → 4-(4-Bromo-phenoxy)-quinoline-2-carboxylic acid ethyl ester

HRID 1431008Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14](Cl)[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1)=[O:5])[CH3:2].[Br:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]([O:24][C:21]2[CH:22]=[CH:23][C:18]([Br:17])=[CH:19][CH:20]=2)[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 4-chloro-quinoline-2-carboxylic acid ethyl ester (910 mg, 3.87 mmol) in DMF (15 ml) was added 4-bromophenol (737 mg, 4.26 mmol), followed by Cs2CO3 (1.89 g, 5.81 mmol). The reaction mixture was then heated to 60° C. for 16 hrs. On the second day the mixture was cooled to r.t. and concentrated down. The residue was partitioned between EtOAc (10 ml) and water (20 ml). The EtOAc layer was separated, dried over MgSO4, filtrated, concentrated, and purified by Biotage with EtOAc/Hexane (15%, 4 CV) to afford 4-(4-bromo-phenoxy)-quinoline-2-carboxylic acid ethyl ester (609 mg, 42.3%). 1H NMR (300 MHz, DMSO-d6): δ 8.36 (m, 1H), 8.18 (m, 1H), 7.93 (m, 1H), 7.80 (m, 1H). 7.75 (m, 2H), 7.34 (m, 2H), 7.14 (s, 1H), 4.34 (m, 2H), 1.30 (m, 3H). LC-MS m/z=373 [C18H14BrNO3+H]+.

Workup

temperatureOn the second day the mixture was cooled to r.t.
concentrationconcentrated down
customThe residue was partitioned between EtOAc (10 ml) and water (20 ml)
customThe EtOAc layer was separated
dry with materialdried over MgSO4
filtrationfiltrated
concentrationconcentrated
custompurified by Biotage with EtOAc/Hexane (15%, 4 CV)

Sources & evidence

ORD record: ord-9bac1b969c4b4219bb8c8e7c0c013dc6
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940927B2

Reaction notes

Loading…