Dimethylformamide → 8-Bromo-5,6-difluorochroman-4-one
Reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:9]=1[O:10][CH2:11][CH2:12][C:13]([OH:15])=O.CN(C=O)C.[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[Br:7][C:8]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[C:16]2[C:9]=1[O:10][CH2:11][CH2:12][C:13]2=[O:15]Participants
Procedure
Oxalyl chloride (1.7 mL, 20 mmol) was added to the solution of 2.8 g (10 mmol) of 3-(2-bromo-4,5-difluorophenoxy)-propanoic acid in 40 mL of anhydrous DCM followed by a drop of DMF. After 1.5 hours, a drying tube was attached and the solution was cooled in an ice-water bath. AlCl3 (1.5 g, 11 mmol) was added and the dark red solution was allowed to slowly reach room temperature while being stirred for 16 hours. The mixture was poured into ice and the organic layer was separated. The aqueous layer was extracted with DCM twice. The combined organic layers were washed with 0.5 N NaOH and brine, then dried over Na2SO4 and concentrated. Column chromatography of this residue with hexane and EtOAc provided 1.9 g of the title compound as an off-white solid (73%). 1H NMR (300 MHz, CDCl3): δ 7.6 (t, 1H), 4.65 (t, 2H), 2.85 (t, 2H).
Workup
- customa drying tube was attached
- temperaturethe solution was cooled in an ice-water bath
- customwas allowed to slowly reach room temperature
- additionThe mixture was poured into ice
- customthe organic layer was separated
- extractionThe aqueous layer was extracted with DCM twice
- washThe combined organic layers were washed with 0.5 N NaOH and brine
- dry with materialdried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-3ac8877836074d60aed05ca5116ccd23
- Source dataset
- uspto-grants-2011_02
- Patent number
- US07884109B2
Reaction notes
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