1-Bromo-2-fluoro-4-methoxybenzene

Clear colorless to light yellow liquid

Into a 250-mL round-bottom flask, was placed 4-bromo-3-fluorophenol (5.0 g, 26.18 mmol, 1.00 equiv), tetrahydrofuran (50 mL). This was followed by the addition of potassium hydroxide (2.94 g, 52.40 mmol, 2.00 equiv) in portions. To this was added CHInto a 250-mL round-bottom flask, was placed 4-bromo-3-fluorophenol (5.0 g, 26.18 mmol, 1.00 equiv), tetrahydrofuran (50 mL). This was followed by the addition of potassium hydroxide (2.94 g, 52.40 mmol, 2.00 equiv) in portions. To this was added CHTo a solution of 4-bromo-3-fluoro-phenol (500 mg, 2.62 mmol) in anhydrousTHF (10 mL) was added sodium hydride (60percent dispersion in mineral oil, 115 mg, 2.88 mmol) portionwise. The reaction mixture was stirred for 20 min before iodomethane (0.500 mL, 8.0 mmol). The resultant mixture was stirred at room temperature for 16 hours before being partitioned between EtOAc and water. The organic layer was separated, washed with a saturated solution of sodium hydrogencarbonate followed by brine, dried (NaA mixture of tert-butyl ((3S, 5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-1-(5-(2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamido)-1H-indol-4-yl)pyrrolidin-3-yl)carbamate (50 mg, 0.072 mmol), General procedure: Benzimidazole (5 mmol), 1-bromo-2-fluorobenzene derivatives (15 mmol, 2 equiv) and tripottasium phosphate (5.31g, 25 mmol, 5 equiv) were dissolved in DMF (30 mL). The mixture was stirred at 150 C. The reaction time was determined by monitoring with TLC. The reaction mixture was diluted with CH2Cl2 (50 mL) and water (50 mL). The phases were separated, and the aqueous layer was extracted with CH2Cl2 (2 × 30 mL). The combined organic layerswere washed with water (3 × 50 mL), dried with MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/AcOEt).

A halo-aryl compound used in the preparation of orally available mGlu1 receptor enhancers.

Molecular Weight:205.02
XLogP3:2.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:203.95861
Monoisotopic Mass:203.95861
Topological Polar Surface Area:9.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes