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

HRID 41101

反応式

HRID 41101 の反応式
[C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].CS(O[CH2:18][C@H:19]1[O:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]1)(=O)=O.O>CN(C=O)C>[O:6]=[C:4]1[C:3]2[C:2](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:1](=[O:11])[N:5]1[CH2:18][C@H:19]1[O:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:20]1

参加物

5

反応物 3

HCID 962WaterHCID 24194345Phthalimide potassium saltHCID 86673567(S)-tert-butyl 2-((methylsulfonyloxy)methyl)morpholine-4-carboxylate

生成物 1

HCID 67173668(R)-tert-butyl 2-((1,3-dioxoisoindolin-2-yl)methyl)morpholine-4-carboxylate収率 86,388.602%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
112.5 °C

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).

後処理

  1. temperaturecooled to room temperature
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×250 mL)
  3. washThe combined organic layers were then washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was diluted in hexanes (200 mL)
  8. stirringstirred vigorously
  9. additionwhile adding slowly Et2O (100 mL)
  10. filtrationwas filtered on a Buchner funnel
  11. washThe filter cake was washed with hexanes
  12. customdried under reduced pressure
  13. concentrationThe mother liquor was concentrated
  14. customthe crude residue purified by silica gel flash chromatography (10-60% EtOAc in hexanes)
  15. customto produce a second crop of solid

出典と根拠

ORDレコード
ord-1b73258e1e4c43acac61e4392b31b371
出典データセット
uspto-grants-2013_09
特許番号
US08530467B2

関連ノート

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