تفاعل #78996

معادلة التفاعل

ethyl acetate

6-bromo-8-fluoro-4,4-dimethyl-dihydro-benzo[d][1,3]oxazin-2-one

4-fluoro-3-chlorophenyl boronic acid

sodium carbonate

→

6-(3-chloro-4-fluoro-phenyl)-8-fluoro-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one

المردود 66.0%

المذيبات

DME

water

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was cooled to room temperature
2. 2
   غسيلThe organic layer was washed twice with aqueous ammonium chloride (100 mL) and once with brine (100 mL)
3. 3
   تجفيفdried over magnesium sulfate
4. 4
   تركيزconcentrated
5. 5
   أخرىThe residue was purified via chromatography (silica gel, 25% ethyl acetate/hexane)

الإجراء التجريبي

A mixture of 6-bromo-8-fluoro-4,4-dimethyl-dihydro-benzo[d][1,3]oxazin-2-one (0.176 g, 0.64 mmol), 4-fluoro-3-chlorophenyl boronic acid (0.15 g, 0.84 mmol), tetrakis(triphenylphosphine)-palladium (0) (0.04 g, 0.032 mmol), and sodium carbonate (0.20 g, 1.92 mmol) in DME (10 mL) and water (5 mL) was subject to a blanket of nitrogen for 15 minutes at 50° C. and then was heated at 85° C. for 1 hour. The reaction mixture was cooled to room temperature and ethyl acetate (100 mL) was added. The organic layer was washed twice with aqueous ammonium chloride (100 mL) and once with brine (100 mL), dried over magnesium sulfate and concentrated. The residue was purified via chromatography (silica gel, 25% ethyl acetate/hexane) to give 6-(3-chloro-4-fluoro-phenyl)-8-fluoro-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one as a white solid (0.13 g, 66%): mp 246-248° C.; 1H-NMR (DMSO-d6) δ10.5 (s, 1H), 8.00 (dd, 1H, J=7.09, 2.32 Hz), 7.78-7.73 (m, 1H), 7.62 (dd, 1H, J=11.86, 1.77 Hz), 7.7 (t, 2H, J=9 Hz), 1.7 (s, 6H); MS (APCI) m/z 324 ([M+H]+, 100%); Anal. Calc. For C16H12F2NO2.0.5 H2O: C, 57.76; H, 3.94; N, 4.21. Found: C, 57.49; H, 3.69; N, 4.03.

المصدر