反応 #480397

反応方程式

sodium hydroxide

methyl (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop 2-ynyl]-4-[3-(R,S)-amino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

→

(3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-4-[3-(R,S)-amino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylic acid

収率 34.7%

溶媒

isopropyl ether

dioxane

isopropyl ether

反応条件

後処理

1. 1
   濃縮The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
2. 2
   その他The residue obtained
3. 3
   その他is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; mass 40 g), elution
4. 4
   その他a dichloromethane/methanol (80/20 by volume) mixture, a dichloromethane/methanol (60/40 by volume) mixture and a dichloromethane/methanol/triethylamine (74/25/1 by volume) mixture, with 100-cm3 fractions being collected Fractions 16 to 29 (which
5. 5
   濃縮concentrated to dryness under the above conditions
6. 6
   その他The residue obtained
7. 7
   ろ過filtered off
8. 8
   洗浄washed 2 times with 20 cm3 of diethyl ether
9. 9
   その他purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 2.3 cm; mass 25 g), elution
10. 10
    濃縮concentrated to dryness under the above conditions
11. 11
    その他The solid obtained
12. 12
    ろ過filtered off
13. 13
    洗浄washed 3 times with 10 cm3 of pentane
14. 14
    その他dried

実験手順

1.37 cm3 of 5N aqueous sodium hydroxide solution are added with stirring, at a temperature in the region of 20° C., to a solution of 0.9 g of methyl (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop 2-ynyl]-4-[3-(R,S)-amino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 9 cm3 of dioxane and then the combined mixture is brought to a temperature in the region of 60° C. for 16 hours. The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; mass 40 g), elution being carried out with a dichloromethane/methanol (90/10 by volume) mixture, a dichloromethane/methanol (80/20 by volume) mixture, a dichloromethane/methanol (60/40 by volume) mixture and a dichloromethane/methanol/triethylamine (74/25/1 by volume) mixture, with 100-cm3 fractions being collected Fractions 16 to 29 (which contain the purified product) are combined and then concentrated to dryness under the above conditions. The residue obtained is taken up in 30 cm3 of isopropyl ether, filtered off, washed 2 times with 20 cm3 of diethyl ether and then purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 2.3 cm; mass 25 g), elution being carried out with a dichloromethane/methanol (95/05 by volume) mixture. Fractions 4 to 7 are combined and then concentrated to dryness under the above conditions. The solid obtained is taken up in 25 cm3 of isopropyl ether, filtered off, washed 3 times with 10 cm3 of pentane and dried to afford 0.304 g of (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-4-[3-(R,S)-amino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylic acid.

出典