تفاعل #2073968

معادلة التفاعل

3-chloro-1-iodopropane

4-butylpiperidine

NaI

K2CO3

NaH

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

→

title compound

المردود 76.7%

1-[3-(4-Butylpiperidin-1-yl)propyl]-6-fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one

المردود 76.7%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGby stirring at r.t for 20 h
2. 2
   أخرىThe reaction mixture was quenched with water
3. 3
   استخلاصthe product extracted into EtOAc
4. 4
   تجفيفThe combined organic layers were dried over Na2SO4
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated
7. 7
   workup.DISSOLUTIONThe crude material was dissolved in MeCN (2 mL)
8. 8
   workup.STIRRINGshaken at 50° C. for 20 h
9. 9
   أخرىThe reaction mixture was quenched with water
10. 10
    استخلاصthe product extracted into EtOAc
11. 11
    تجفيفThe combined organic layers were dried over Na2SO4
12. 12
    ترشيحfiltered
13. 13
    تركيزconcentrated
14. 14
    أخرىThe residue was purified by cation exchange CC

الإجراء التجريبي

A reaction flask was charged with 6-fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one (0.150 g, 0.84 mmol) in dry DMF (1 mL) under N2. NaH (60% in oil, 0.038 g, 0.92 mmol) was added and stirred at rt for 30 min. Then 3-chloro-1-iodopropane (0.131 g, 0.84 mmol) was added followed by stirring at r.t for 20 h. The reaction mixture was quenched with water and the product extracted into EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude material was dissolved in MeCN (2 mL) followed by addition of 4-butylpiperidine (0.085 g, 0.6 mmol), NaI (0.150 g, 1.0 mmol), and K2CO3 (0.138 g, 1.0 mmol) and shaken at 50° C. for 20 h. The reaction mixture was quenched with water and the product extracted into EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by cation exchange CC followed by flash CC (SiO2; EtOAc) to give the title compound (107LH93-1) (0.166 g, total yield 55%). 1H NMR (CH3OD) δ 7.00 (d, J=6.4 Hz, 1H), 6.88 (d, J=9.2 Hz, 1H), 3.98-3.91 (m, 2H), 2.93-2.86 (m, 2H), 2.85-2.78 (m, 2H), 2.58-2.52 (m, 2H), 2.40-2.43 (m, 2H), 2.25 (d, J=2.0 Hz, 3H), 1.98-1.76 (m, 4H), 1.70-1.62 (m, 2H), 1.35-1.22 (m, 9H), 0.88 (t, J=7.0 Hz, 3H); 13C NMR (CH3OD) δ 171.1, 157.2 (d, J=241 Hz), 135.1 (d, J=3 Hz), 126.5 (d, J=8 Hz), 123.2 (d, J=18 Hz), 118.1 (d, J=5 Hz), 114.3 (d, J=24 Hz), 55.8, 43.9, 40.4, 36.2, 35.7, 32.0, 31.5, 29.0, 24.6, 24.3, 22.8, 13.4 (br).

المصدر