Citric Acid → 1'-[4-(2-hydroxyethoxy)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 422870노트

반응식

HRID 422870 반응식
[O:1]=[C:2]1[C:10]2([C:22]3[C:13](=[CH:14][C:15]4[O:20][CH2:19][CH2:18][O:17][C:16]=4[CH:21]=3)[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:23][C:24]1[CH:36]=[CH:35][C:27]([O:28][CH2:29][C:30](OCC)=[O:31])=[CH:26][CH:25]=1.[BH4-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>COCCOC>[OH:31][CH2:30][CH2:29][O:28][C:27]1[CH:26]=[CH:25][C:24]([CH2:23][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]3([C:22]4[C:13](=[CH:14][C:15]5[O:20][CH2:19][CH2:18][O:17][C:16]=5[CH:21]=4)[O:12][CH2:11]3)[C:2]2=[O:1])=[CH:36][CH:35]=1

참가 물질

5

반응물 3

HCID 311Citric AcidHCID 4148881Lithium borohydrideHCID 45280338ethyl {4-[(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)methyl]phenoxy}acetate

생성물 1

HCID 452803401'-[4-(2-hydroxyethoxy)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one수율 63%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

실험 절차

To a solution of ethyl {4-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]phenoxy}acetate (0.22 g, 0.44 mmol) in anhydrous 1,2-dimethoxyethane (5 mL) was added at 0° C. lithium borohydride (2.0 M solution in tetrahydrofuran, 0.44 mL, 0.88 mmol) dropwise. The mixture was stirred at ambient temperature for 2 h, cooled to 0° C., and 7% w/v aqueous citric acid (15 mL) was added dropwise. The mixture was extracted with chloroform (3×60 mL). The combined organic layers was washed with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 50% ethyl acetate in hexanes to afford 1′-[4-(2-hydroxyethoxy)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.12 g, 63%) as a colorless solid: mp 196-197° C.; 1H NMR (300 MHz, CDCl3) δ 7.31-7.24 (m, 2H), 7.23-7.12 (m, 2H), 7.05-6.97 (m, 1H), 6.92-6.86 (m, 2H), 6.83-6.78 (m, 1H), 6.51 (s, 1H), 6.22 (s, 1H), 4.89 (ABq, J=79.6, 15.4 Hz, 2H), 4.79 (ABq, J=83.8, 8.9 Hz, 2H), 4.22-4.08 (m, 4H), 4.08-3.91 (m, 4H), 1.94 (s, 1H); 13C NMR (300 MHz, CDCl3) δ 177.5, 158.2, 155.2, 144.6, 142.0, 138.2, 132.3, 128.8, 128.7, 128.2, 123.8, 123.3, 121.0, 114.9, 111.5, 109.3, 99.4, 80.1, 69.1, 64.5, 63.9, 61.4, 58.0, 43.6; MS (ES+) m/z 446.0 (M+1).

후처리

  1. temperaturecooled to 0° C.
  2. additionwas added dropwise
  3. extractionThe mixture was extracted with chloroform (3×60 mL)
  4. washThe combined organic layers was washed with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluted with 50% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-6c9e5d4a5c9241008d298327c71d87d2
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101647B2

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