ChemicalBook CAS DataBase List 5-Bromo-2-fluorophenol

5-Bromo-2-fluorophenol synthesis

5synthesis methods

Product Name:5-Bromo-2-fluorophenol
CAS Number:112204-58-7
Molecular formula:C6H4BrFO
Molecular Weight:191

460-00-4 Synthesis

460-00-4
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$6.00/10g

112204-58-7
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$10.00/5g

Yield:112204-58-7 85%

Reaction Conditions:

Stage #1:1-Bromo-4-fluorobenzene with 2,2,6,6-tetramethyl-piperidine;n-butyllithium in tetrahydrofuran;hexane at -78;
Stage #2: with Trimethyl borate in tetrahydrofuran;hexane at -78 - 20; for 2.5 h;

Steps:

7A
To a solution of 2,2,6,6-tetramethyl piperidine (5.6 mL, 33.2 mmol) in THF at -20° C. was added n-BuLi (1.6 M in hexanes, 18.8 mL, 30 mmol). The mixture was stirred at -20° C. for 10 min before it was cooled to -78° C. 1-Bromo-4-fluorobenzene (2.95 mL, 27 mmol) was added over 10 min and the mixture was stirred at -78° C. for 2.0 h before trimethyl borate (6.0 mL, 54 mmol) was added. The mixture was stirred at -78° C. for 30 min and then at rt for 2.0 h. After it was cooled back to 0° C., glacial acetic acid (4.86 mL, 81 mmol) was added and stirred for 30 min, followed by addition of 30% H₂O₂(4.86 mL, 81 mmol). The mixture was stirred at rt for 24 h, quenched by addition of MnO₂(40 mg). After stirring at rt for 30 min, the cloudy solution was filtered through a pad of wet Celite and extracted with EtOAc. The EtOAc layer was washed with aquous NaHSO₃, brine and dried over Na₂SO₄. The crude residue was purified by flash column chromatography (EtOAc:hexanes=1:5) to give 4.4 g (85%) of 7A as a liquid. ¹H NMR (400 MHz, CDCl₃) δ ppm 5.39 (s, 1H) 6.90-6.98 (m, 2H) 7.14 (dd, J=8.13, 1.98 Hz, 1H).

References:

Bristol-Myers Squibb Company US2010/227894, 2010, A1 Location in patent:Page/Page column 27

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