反応 #93056

反応方程式

3-carboxyethyl-4-chloroquinoline

ammonia

4-dimethylamino-1-methylamino-2-butanol

potassium hydride

tetrahydrofuran

→

final product

2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methyl-1,4-oxazepino[6,7-c]quinolin-5(4H)-one

溶媒

methanol

ethyl acetate

water

反応条件

後処理

1. 1
   その他of 30 min
2. 2
   その他to quench
3. 3
   その他the reaction
4. 4
   その他the mixture was partitioned between isopropanol ether and water
5. 5
   抽出The aqueous layer was extracted again with two 70 ml portions of isopropyl ether
6. 6
   抽出The aqueous layer was then continuously extracted for 15 hr with chloroform
7. 7
   その他The chloroform layer was collected
8. 8
   ろ過filtered
9. 9
   濃縮concentrated by rotary evaporation at 80°
10. 10
    その他The crude material (18 g) was purified by HPLC
11. 11
    その他Approximately 4 g (b 15.6%) of product was obtained on evaporation of fractions

実験手順

To a suspension of 19.4 g (35% in oil, 0.172 mole) of potassium hydride in 150 ml of tetrahydrofuran was added at a rapid drop, 12.4 g (0.086 mole) of 4-dimethylamino-1-methylamino-2-butanol. After 10 min., 20 g (0.086 mole) of 3-carboxyethyl-4-chloroquinoline was added via a powder dropping funnel over a period of 30 min. The mixture was stirred at room temperature overnight. Approximately 50 ml of water was added to quench the reaction and the mixture was partitioned between isopropanol ether and water. The aqueous layer was extracted again with two 70 ml portions of isopropyl ether. The aqueous layer was then continuously extracted for 15 hr with chloroform. The chloroform layer was collected, filtered and concentrated by rotary evaporation at 80°, 30 mm. The crude material (18 g) was purified by HPLC using silica gel as the stationary phase and 3% triethylamine/ethanol as the eluent. Approximately 4 g (b 15.6%) of product was obtained on evaporation of fractions having a similar thin layer chromatograph (TLC) using ethyl acetate, methanol and aqueous conc. ammonia (7:2:1 parts by volume respectively) on silica. TLC of the final product using the same solvent mix on silica was identical to that of the free base of the same compound prepared in Example 2. C.I. mass spec showed M+H of 300. The oxalate salt was also identical to that obtained in Example 2.

出典