2-BROMO-4-ETHYLPHENOL

Bromine (11. 6mL, 0. 23MOL) was added slowly to a cooled 0 C of 4-ethylphenol (25g, 0. 21 mol) dissolved IN CH2CI2 (125mL). After the addition was complete the reaction mixture was stirred for 5 mins and then quenched with 1 N NAOH. The reaction mixture was diluted with H20 and the layers separated. The organic layer was concentrated to an orange oil. Purification by flash column chromatography (0percent to 5percent EtOAc in hexanes) gave the title compound as a clear oil (42g, 98percent). 1H NMR (400 MHz, CDCl3) : 5 1.20 (t, J=7. 6 Hz, 3 H), 2.58 (q, J=7. 5 Hz, 2 H), 5.36 (s, 1 H), 6.93 (d, J=8. 3 Hz, 1 H), 7.03 (d, J=8. 3 Hz, 1 H), 7.28 (s, 1 H).Bromine (11.6 mL, 0.23 mol) was added slowly to a cooled 0° C. of 4-ethylphenol (2 g, 0.21 mol) dissolved in CHGeneral procedure: To a solution of 4-alkylphenol (20 mmol) in chloroform (20 mL), sodium hydrogencarbonate (2 g, 24 mmol) was added. The resulting suspension was cooled to 0°C. While a solution of elementary bromine (1.12 mL, 22 mmol) in chloroform (8 mL) was slowly added, the suspension was vigorously stirred. After completion of the reaction, monitored by TLC the suspension was filtered. The filter with the solid residue was rinsed once with 50 mL of chloroform. The combined organic solutions were evaporated under reduced pressure. The final workup of the product was done either by distillation or by column chromatography (petroleum ether : ethyl acetate, 9 : 1).Example 30 3-F 4- [3- ()- (4-ETHYL-2-THIOPHEN-2-YL-PHENOXY)-BUTOXY]-2-METHYL-PHENYL}-PROPIONIC ACID Step A 2-BROMO-4-ETHYL-PHENOL; N-bromosuccinimide (1. 58 g, 8.92 mmol) is added to a solution of 4-ethyl phenol (1.0 g, 8.19 mmol) in ACN (35 mL), and the mixture is stirred under N2 at ambient temperature. After 24 h, the mixture is concentrated under reduced pressure and diluted with water. The mixture is extracted with EtOAc, and organic phases are washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography, silica, hexanes: EtOAc (95: 5) yields title compound (1.01 g, 4.9 mmol, 61percent): RF 0.34 hexanes: EtOAc (90: 10), 1H NMR (400 MHz, CDC13) 7.28 (d, 1H, J= 2. 4 Hz), 7.03 (dd, 1H, JL= 2.4 Hz, J2= 8.4 Hz), 6. 92 (d, 1H, J= 8. 4 Hz), 5.34 (s, 1H), 2.56 (q, 2H, J = 7.6 Hz), 1.20 (t, 3H, J= 7. 6 Hz).To a solution of 4-ethylphenol (1.0 g, 8.2 mmol, 1.0 eq) in dry acetonitrile (40 mL) was added NBS (1.46 g, 8.2 mmol, 1.0 eq). The mixture was allowed to stir at RT for 2 h followed by removal of acetonitrile. The residue was redissolved in Et20 and washed with H20. The organic extracts were dried over Na2S04, filtered, and concentrated. The crude material was purified by flash chromatography (Biotage FLASH 40S KP-Sil silica, 5percent Et20/hexanes) to yield 1.0 g (52percent) of 16 as a clear oil.

Molecular Weight:201.06
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:199.98368
Monoisotopic Mass:199.98368
Topological Polar Surface Area:20.2
Heavy Atom Count:10
Complexity:105
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes