反応 #69379

反応方程式

Potassium phthalimide

(S)-tert-butyl 2-((methylsulfonyloxy)methyl)morpholine-4-carboxylate

water

→

title compound

(R)-tert-butyl 2-((1,3-dioxoisoindolin-2-yl)methyl)morpholine-4-carboxylate

溶媒

DMF

反応条件

後処理

1. 1
   温度cooled to room temperature
2. 2
   抽出The aqueous layer was extracted with CH2Cl2 (3×250 mL)
3. 3
   洗浄The combined organic layers were then washed with brine
4. 4
   乾燥dried over MgSO4
5. 5
   ろ過filtered
6. 6
   濃縮concentrated under reduced pressure
7. 7
   workup.ADDITIONThe residue was diluted in hexanes (200 mL)
8. 8
   workup.STIRRINGstirred vigorously
9. 9
   workup.ADDITIONwhile adding slowly Et2O (100 mL)
10. 10
    ろ過was filtered on a Buchner funnel
11. 11
    洗浄The filter cake was washed with hexanes
12. 12
    その他dried under reduced pressure
13. 13
    濃縮The mother liquor was concentrated
14. 14
    その他the crude residue purified by silica gel flash chromatography (10-60% EtOAc in hexanes)
15. 15
    その他to produce a second crop of solid

実験手順

Potassium phthalimide (28.4 g 0.15 mol) was added to a solution of (S)-tert-butyl 2-((methylsulfonyloxy)methyl)morpholine-4-carboxylate (37.7 g, 0.13 mmol) in DMF (256 mL). The resulting mixture was stirred at 110-115° C. for 16 hr, and then cooled to room temperature and poured into water (500 mL). The aqueous layer was extracted with CH2Cl2 (3×250 mL). The combined organic layers were then washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was diluted in hexanes (200 mL) and then stirred vigorously while adding slowly Et2O (100 mL). The oil turned into a solid, which was filtered on a Buchner funnel. The filter cake was washed with hexanes and dried under reduced pressure. The mother liquor was concentrated, and the crude residue purified by silica gel flash chromatography (10-60% EtOAc in hexanes) to produce a second crop of solid. Both solids were combined to provide the title compound (38.9 g, 88%). 1H NMR (300 MHz, CDCl3) δ ppm 1.45 (s, 9 H), 2.68-2.82 (m, 1H), 2.91-3.04 (m, 1H), 3.44 (dt, J=11.45, 2.81 Hz, 1H), 3.63-3.79 (m, 3H), 3.82-4.03 (m, 3H), 7.70-7.78 (m, 2H), 7.84-7.88 (m, 2H).

出典