Toluene → 5-Bromo-2-(6-chloropyridin-3-yloxy)benzoic acid
Reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[OH:12][C:13]1[CH:14]=[CH:15][C:16]([Cl:19])=[N:17][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>CCOC(C)=O>[Br:11][C:8]1[CH:9]=[CH:10][C:2]([O:12][C:13]2[CH:18]=[N:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]Participants
Conditions
- Temperature
- 105 °C
Procedure
A RBF was charged with 2,5-dibromobenzoic acid (1244 g, 4.44 mol), 5-hydroxy-2-chloropyridine (663.3 g, 5.12 mol) and cesium carbonate (2893.3 g, 8.88 mol). The resulting mixture was stirred for 20 minutes under nitrogen atmosphere at which time copper (I) trifloromethanesulfonate toluene complex (59.7 g, 0.115 mol), toluene (9 L) and EtOAc (39 mL) were added in sequence. The resulting suspension was heated to 105° C. for 2 h and cooled to RT. The toluene was decanted and water (8 L) and EtOAc (8 L) were added to the residue. The mixture was stirred until the solids were completely dissolved. The organic layer was separated and the pH of the aqueous layer was adjusted to pH 2˜3 with 6N HCl. This mixture was then extracted with EtOAc (3×5 L). The combined organic layers were dried over Na2SO4, filtered and concentrated to give 1.28 kg of 5-bromo-2-(6-chloropyridin-3-yloxy)benzoic acid as brown solid, which was used in next step without further purification.
Workup
- additionwere added in sequence
- temperaturecooled to RT
- customThe toluene was decanted
- additionwater (8 L) and EtOAc (8 L) were added to the residue
- dissolutionwere completely dissolved
- customThe organic layer was separated
- extractionThis mixture was then extracted with EtOAc (3×5 L)
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-cb20a6c010f7484388f0e31681401120
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346827B2
Reaction notes
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