反応 #1340616

反応方程式

7-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

triethylamine

(3S,4S)-1-(benzyloxycarbonyl)-3-(tert-butoxycarbonylamino)-4-ethylpyrrolidine

→

title compound

収率 50.1%

7-[(3S,4S)-3-Amino-4-ethylpyrrolidine-1-yl]-1-[(1R,2S)-2-fluorocyclopropyl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

収率 50.1%

溶媒

methanol

反応条件

後処理

1. 1
   ろ過After filtration
2. 2
   濃縮the filtrate was concentrated under reduced pressure
3. 3
   workup.DISSOLUTIONThe obtained residue was dissolved in dimethyl sulfoxide (3 mL)
4. 4
   濃縮The reaction mixture was concentrated under reduced pressure
5. 5
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate (50 mL)
6. 6
   洗浄The solution was washed sequentially with a 10% aqueous citric acid solution (30 mL), water (30 mL×2), and saturated brine (30 mL)
7. 7
   乾燥by drying over anhydrous sodium sulfate
8. 8
   ろ過After filtration
9. 9
   濃縮the filtrate was concentrated under reduced pressure
10. 10
    workup.ADDITIONSubsequently, concentrated hydrochloric acid (2 mL) was added to the obtained residue at room temperature
11. 11
    その他the resultant mixture was transferred to a separatory funnel with water (20 mL)
12. 12
    洗浄by washing by chloroform (30 mL×2)
13. 13
    温度under cooling with ice
14. 14
    抽出the resultant mixture was extracted with chloroform (100 mL×3)
15. 15
    乾燥The combined organic layer was dried over anhydrous sodium sulfate
16. 16
    その他the solvent was removed under reduced pressure
17. 17
    その他The obtained residue was recrystallized from hot ethanol
18. 18
    その他dried under reduced pressure

実験手順

A 10% palladium carbon catalyst (27 mg) was added to a solution of (3S,4S)-1-(benzyloxycarbonyl)-3-(tert-butoxycarbonylamino)-4-ethylpyrrolidine (270 mg, 775 μmol) in methanol (7.75 mL), and the resultant mixture was stirred under a hydrogen atmosphere at room temperature for 15 hours. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in dimethyl sulfoxide (3 mL), and 7-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (216 mg, 775 μmol) and triethylamine (130 μL, 930 μmol) were added to the solution, followed by stirring in an oil bath at 65° C. for 8 days. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (50 mL). The solution was washed sequentially with a 10% aqueous citric acid solution (30 mL), water (30 mL×2), and saturated brine (30 mL), followed by drying over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Subsequently, concentrated hydrochloric acid (2 mL) was added to the obtained residue at room temperature, and the resultant mixture was transferred to a separatory funnel with water (20 mL), followed by washing by chloroform (30 mL×2). The pH of the obtained aqueous layer was adjusted to 12.0 with a 10 mol/L aqueous sodium hydroxide solution under cooling with ice. The pH was adjusted again to 7.4, and the resultant mixture was extracted with chloroform (100 mL×3). The combined organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The obtained residue was recrystallized from hot ethanol, and dried under reduced pressure, to thereby yield the title compound as pale yellow crystals (145 mg, 50.1%).

出典