1-Chloro-2-fluoro-4-Methoxy-5-nitrobenzene

To a solution of 4-chloro-5-fluoro-2-nitrophenol (10.00 g, 52.21 mmol) in dry DMF(50 mL), K2C03 was added (11.00, 79.60 mmol), followed by iodomethane (4.00 mL, 64.25 mmol) and the resulting suspension was stirred at rt for 2.5 days. The resultingdark orange suspension was concentrated in vacuo to remove the DMF solvent, and the residue partitioned between EtOAc (300 mL) and iN HC1 (100 mL). The resulting wasseparated and the organic layer washed successively with 1M NaOH (100 mL), water(100 mL) and brine (100 mL), dried over Na2SO4, filtered and evaporated to give 10.34g of intermediate 86 (96percent yield, dark orange solid).4-Chloro-5-fluoro-2-nitrophenol (2.29 g, 12.0 mmol) was dissolved in DMF (25 mL). KTo 1- chloro-2-fluoro-4-methoxybenzene (5.00 g, 31.2 mmol) in cone. HTo a mixture of 1-chloro-2-fluoro-4-methoxybenzene (5.00 g, 31.1 mmol) in cone. H2S04 (30 mL) at 0-10eC was added portionwise potassium nitrate (3.78 g, 37.4 mmol) and the reaction was stirred at OeC for 2 h. The reaction was quenched with ice water and filtered. The obtained solids were recrystallized with hexanes to give 4.50 g 3 (70percent) of 1-chloro-2-fluoro-4-methoxy-5-nitrobenzene. 1HNMR (400 MHz, DMSO- d6) U8.30 (d, J = 2.0 Hz, 1H), 7.61 (d, J = 2.3 Hz, 1H), 3.96 (s, 3H); ESI-MS (m/z) 205.76 (MH)+.To a mixture of potassium tert-butoxide (3.0 g, 26.9 mmol) in DMF (20 mL), methanol (0.79 g, 24.8 mmol) was added at 0°C. The reaction mixture was stirred at 0°C for 15 minutes then a solution of 1-chloro-2, 4-difluoro-5-nitrobenzene (4.0 g, 20.7 mmol) in DMF (20 mL) was added at 0 °C and the reaction mass stirred for 3 hours at room temperature. Water (200 mL) was added to the reaction mixture and reaction mass was extracted with EtOAc (3 x 50 mL). The combined organic extracts were washed with water (80 mL), brine (80 mL), dried (Na1-methyl-4-(2-methylpiperidin-4-yl)piperazine 197 mg (1 mmol), Put piperidin-4-one 99 mg (1 mmol) and 170 mg (1 mmol) of 4- (piperidin-4-yl) morpholine and 205 mg (1 mmol) of

Molecular Weight:205.57
XLogP3:2.5
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:204.9941989
Monoisotopic Mass:204.9941989
Topological Polar Surface Area:55
Heavy Atom Count:13
Complexity:199
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes