反应详情

温度

65 °C

[(S)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-4-hydroxybutyl]carbamic acid tert-butyl ester (128 mg, 0.301 mmol) obtained in Step 1 above was dissolved in dichloromethane (2.0 ml), and then methanesulfonyl chloride (35 μl, 0.452 mmol) and triethylamine (84 μl, 0.603 mmol) were added thereto at 0° C. After stirring for one hour, a saturated aqueous sodium bicarbonate solution (5 ml) and water (15 ml) were added to the mixture. The solution was extracted three times with dichloromethane (20 ml). The dichloromethane solutions were combined together and sequentially washed with a saturated aqueous sodium chloride solution, 0.1N hydrochloric acid, and a saturated aqueous sodium chloride solution. The washed dichloromethane solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was dissolved in tetrahydrofuran (2.0 ml), and then morpholine (105 μl, 1.21 mmol) was added thereto. The mixture was heated at 65° C. for 16 hours. Water (5 ml) and 1N hydrochloric acid (1 ml) were added to the reaction solution, and washed with ethyl acetate (5 ml). A saturated aqueous sodium bicarbonate solution (20 ml) was added to the washed aqueous solution. The mixture was extracted three times with ethyl acetate (25 ml) and then three times with dichloromethane (25 ml). The ethyl acetate/dichloromethane solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to yield ((S)-3-amino-4-morpholin-4-ylbutyl)carbamic acid tert-butyl ester (24 mg) as a colorless oily material.

1. customat 0° C
2. extractionThe solution was extracted three times with dichloromethane (20 ml)
3. washsequentially washed with a saturated aqueous sodium chloride solution, 0.1N hydrochloric acid
4. dry with materialThe washed dichloromethane solution was dried over anhydrous sodium sulfate
5. filtrationAfter filtration
6. concentrationthe filtrate was concentrated under reduced pressure
7. dissolutionThe resulting crude product was dissolved in tetrahydrofuran (2.0 ml)
8. washwashed with ethyl acetate (5 ml)
9. additionA saturated aqueous sodium bicarbonate solution (20 ml) was added to the washed aqueous solution
10. extractionThe mixture was extracted three times with ethyl acetate (25 ml)
11. dry with materialThe ethyl acetate/dichloromethane solution was dried over anhydrous sodium sulfate
12. filtrationAfter filtration
13. concentrationthe filtrate was concentrated under reduced pressure