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 422870Notes

Reaction equation

HRID 422870 reaction equation
[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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6c9e5d4a5c9241008d298327c71d87d2
Source dataset
uspto-grants-2012_01
Patent number
US08101647B2

Reaction notes

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