تفاعل #69379

معادلة التفاعل

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

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooled to room temperature
2. 2
   استخلاصThe aqueous layer was extracted with CH2Cl2 (3×250 mL)
3. 3
   غسيلThe combined organic layers were then washed with brine
4. 4
   تجفيفdried over MgSO4
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated 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
    ترشيحwas filtered on a Buchner funnel
11. 11
    غسيلThe filter cake was washed with hexanes
12. 12
    أخرىdried under reduced pressure
13. 13
    تركيزThe mother liquor was concentrated
14. 14
    أخرىthe crude residue purified by silica gel flash chromatography (10-60% EtOAc in hexanes)
15. 15
    أخرىto produce a second crop of solid

الإجراء التجريبي

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).

المصدر