Citric Acid → 2-Bromo-1-(cyclobutyloxy)-4-(trifluoromethoxy)benzene

HRID 1420819Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[OH:13].[CH:14]1(Br)[CH2:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[Br:1][C:2]1[CH:7]=[C:6]([O:8][C:9]([F:11])([F:12])[F:10])[CH:5]=[CH:4][C:3]=1[O:13][CH:14]1[CH2:17][CH2:16][CH2:15]1

Participants

Conditions

Temperature: 50 °C

Procedure

2-Bromo-4-(trifluoromethoxy)phenol (Description 11; 1.5 g, 5.83 mmol) and cyclobutyl bromide (3.0 g, 17.5 mmol) were dissolved in dimethylformamide (10 ml). Potassium carbonate (4.85 g, 35 mmol) was added and the solution was stirred at 50° C. for 16 h. The solution was allowed to cool to ambient temperature, poured into a 10% citric acid solution (50 ml) and extracted with ethyl acetate (2×100 ml). The combined organic layers were washed with water and dried over sodium sulphate. Removal of the solvent in vacuo gave an oil which was chromatographed on silica in 10% ethyl acetate/hexane to give the title compound as an oil (1.65 g, 91%). 1H NMR (250 MHz, CDCl3) δ7.44-7.42 (1H, m), 7.12-7.07 (1H, m), 6.73-6.70 (1H, d, J 9.0 Hz), 4.71-4.60 (1H, m), 2.52-2.41 (2H, m), 2.30-2.18 (2H, m), and 1.92-1.55 (2H, m).

Workup

temperatureto cool to ambient temperature
extractionextracted with ethyl acetate (2×100 ml)
washThe combined organic layers were washed with water
dry with materialdried over sodium sulphate
customRemoval of the solvent in vacuo
customgave an oil which
customwas chromatographed on silica in 10% ethyl acetate/hexane

Sources & evidence

ORD record: ord-7ad5ab7cb5ca4ad9a0fe1c0bd42303ce
Source dataset: uspto-grants-2000_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06071927

Reaction notes

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