تفاعل #2189691

معادلة التفاعل

HCl

3-Chloro-N-(4-fluoro-3-methyl-phenyl)-propionamide

3-chloropropionyl chloride

K2CO3

AlCl3

→

6-fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one

المردود 14.0%

6-fluoro-5-methyl-3,4-dihydro-1H-quinolin-2-one

المردود 4.0%

المذيبات

CH3CN

EtOAc

ظروف التفاعل

المعالجة

1. 1
   غسيلwashed with water (20 mL), HCl (20 mL, 4N) and brine (20 mL)
2. 2
   تجفيفThe organic phase was dried with Na2SO4
3. 3
   ترشيحfiltered
4. 4
   تركيزconcentrated under reduced pressure
5. 5
   درجة الحرارةThe residue (5.9 g) was heated to 135° C.
6. 6
   درجة الحرارةthe reaction was then cooled to 50° C.
7. 7
   workup.STIRRINGthe resulting mixture was stirred for 15 min
8. 8
   استخلاصThe mixture was extracted with EtOAc (50 mL)
9. 9
   غسيلthe organic phase was washed with water (20 mL)
10. 10
    تجفيفThe resulting organic phase was dried (Na2SO4)
11. 11
    ترشيحfiltered
12. 12
    تركيزconcentrated under reduced pressure
13. 13
    أخرىpurified by prep HPLC

الإجراء التجريبي

3-Chloro-N-(4-fluoro-3-methyl-phenyl)-propionamide (3.8 g, 30 mmol), 3-chloropropionyl chloride (2.9 mL, 30 mmol) and K2CO3 (5.0 g, 36 mmol) were added to CH3CN (50 mL) and the mixture was stirred for 44 h at rt. Thereafter, the reaction was diluted with EtOAc (50 mL) and washed with water (20 mL), HCl (20 mL, 4N) and brine (20 mL). The organic phase was dried with Na2SO4, filtered and concentrated under reduced pressure. The residue (5.9 g) was heated to 135° C. and small portions of AlCl3 (11 g, 82 mmol) were added during 30 min, the reaction was then cooled to 50° C. and HCl (4N 20, mL) was added and the resulting mixture was stirred for 15 min. The mixture was extracted with EtOAc (50 mL) and the organic phase was washed with water (20 mL). The resulting organic phase was dried (Na2SO4), filtered concentrated under reduced pressure and purified by prep HPLC to yield 6-fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one (0.76 g, 14%) and 6-fluoro-5-methyl-3,4-dihydro-1H-quinolin-2-one (0.190 g, 4%). 6-Fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one (107LH75-1). 1H NMR (CDCl3) δ 8.86 (brs, 8.86, 1H), 6.81 (d, J=9.2 Hz, 1H), 6.62 (d, J=6.8 Hz, 1H), 2.91 (brt, J=7.6 Hz, 3H), 2.94-2.87 (m, 2H), 2.20 (d, J=2.0 Hz). 6-Fluoro-5-methyl-3,4-dihydro-1H-quinolin-2-one (107LH75-2). 1H NMR (CDCl3) δ 8.78 (brs, 1H), 6.85 (t, J=8.8 Hz, 1H), 6.62 (dd, J=4.5, 8.8 Hz, 1H), 2.92 (brt, J=7.6 Hz, 2H), 2.64-2.58 (m, 2H), 2.20 (d, J=2.4 Hz, 3H).

المصدر