2-Chloro-6-fluorophenol

Solid

(0.5 mg, 3.5mmol) and hexamethylenetetramine (0.5 g, 3.5 mmol) were dissolved in TFA (3 mL) and stirred at 60 C for 16 h. The mixture was poured into ice -water (20 mL) and extracted with Et20 (3 x 20 mL). The organic fractions were combined, washed with brine (25 mL), dried over MgSCf, filtered, and the solvent was evaporated. The product, purified by column chromatography (hexane :EtO Ac; 7:3), was obtained as a white solid (250 mg, 40 %). (0157) NMR (500 MHz, CDCfs) (ppm) 9.83 (d, / = 2.1 Hz, 1H), 7.74 - 7.71 (m, 1H), 7.59 (dd, / = 9.6, 1.8 Hz, 1H), 6.12 (s, 1H); (0158) 13C NMR (126 MHz, CDCf) (ppm) 188.8, 151.6 (d, / = 248.2 Hz), 146.2 (d, / = 15.3 Hz), 129.7 (d, / = 5.4 Hz), 127.5 (d, / = 3.1 Hz), 122.7, 115.4 (d, / = 18.5 Hz); 19F NMR (471 MHz, CDCl3) (0159) HRMS calcd for C7H3CIFO2 [ M-I I f 172.9811, found 172.9809.(Synthesis of Compound 2-40) 3-Fluoro-2-hydroxychlorobenzene (33.0 g) in a reaction vessel equipped with a stirrer, a thermometer, a dropping funnel, and a condenser under a nitrogen atmosphere.Bis (ditertiary butyl (4-dimethylaminophenyl) phosphine) palladium (II) chloride complex (3.0 g), THF (100 ml) and 2 M aqueous potassium carbonate solution (180 ml) were added, and the temperature was raised to 60 C. while stirring. .To the reaction mixture was added dropwise 2, 3-difluoro-4-butoxyphenylboronic acid (23.1 g) previously dissolved in THF (70 ml). After stirring at 60 C. for 7 hours, the heating was stopped and the solution temperature was returned to room temperature. Thereafter, 10% hydrochloric acid (150 ml) was added. The organic layer was separated, and the aqueous layer was re-extracted with toluene (150 ml).The obtained organic layer was combined, then washed sequentially with water and saturated brine, and dried by adding anhydrous sodium sulfate. The resulting solution was concentrated, toluene (170 ml) was added and the dissolved solution was passed through a column packed with silica gel (40 g) and then toluene (240 ml). The resulting column-passing solution was concentrated to give compound 2-40 (36.6 g).

Used as pharmaceutical intermediate

Molecular Weight:146.54
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:145.9934706
Monoisotopic Mass:145.9934706
Topological Polar Surface Area:20.2
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes