反応 #481898

反応方程式

4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl)piperidine-3-carboxylate dihydrochloride

potassium carbonate

potassium iodide

2-(2-bromoethylthio)thiophene

→

methyl (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-carboxylate

溶媒

acetonitrile

DMF

acetonitrile

triethylamine

反応条件

後処理

1. 1
   温度After cooling to about 20° C.
2. 2
   ろ過the reaction mixture was filtered on sintered glass
3. 3
   濃縮concentrated under reduced pressure (5 kPa)
4. 4
   その他The organic phase was separated
5. 5
   洗浄washed with twice 75-cm3 of a saturated aqueous sodium chloride solution
6. 6
   乾燥dried over magnesium sulfate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
9. 9
   その他The residue obtained
10. 10
    その他was purified by chromatography, under a nitrogen pressure of 50 kPa
11. 11
    洗浄on a column of silica gel (particle size 20-45 μ; diameter 2 cm; height 40 cm), eluting with a mixture of cyclohexane-ethyl acetate (25/75 by volume)
12. 12
    その他collecting 50-cm3 fractions
13. 13
    濃縮Fractions 6 to 8 were concentrated

実験手順

0.74-cm3 of triethylamine was added to a solution composed of 1.17 g of methyl (3RS, 4RS) 4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl)piperidine-3-carboxylate dihydrochloride in 20-cm3 of acetonitrile and 10-cm3 of DMF, followed by 638 mg of 2-(2-bromoethylthio)thiophene in 10-cm3 of acetonitrile, 1 g of potassium carbonate and 431 mg of potassium iodide. The mixture was stirred for 15 hours at a temperature in the region of 65° C. under an inert atmosphere. After cooling to about 20° C., the reaction mixture was filtered on sintered glass. The filtrate was taken up in 100-cm3of acetonitrile and concentrated under reduced pressure (5 kPa). The residue was taken up in 200-cm3 of ethyl acetate and 100-cm3 of water. The organic phase was separated after settling out, washed with twice 75-cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ; diameter 2 cm; height 40 cm), eluting with a mixture of cyclohexane-ethyl acetate (25/75 by volume) and collecting 50-cm3 fractions. Fractions 6 to 8 were concentrated. 630 mg of methyl (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-carboxylate were obtained in the form of a colorless oil.

出典