Lithium hydroxide, monohydrate → {3-[(2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-1'(2'H)-yl)methyl]phenoxy}acetic acid

HRID 422867Notes

Reaction equation

HRID 422867 reaction equation
[O:1]=[C:2]1[C:10]2([CH2:14][O:13][C:12]3[CH:15]=[C:16]4[C:20](=[CH:21][C:11]2=3)[CH2:19][CH2:18][O:17]4)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][C:23]1[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=1)[O:26][CH2:27][C:28]([O:30]CC)=[O:29].O.[OH-].[Li+]>O1CCCC1.O>[O:1]=[C:2]1[C:10]2([CH2:14][O:13][C:12]3[CH:15]=[C:16]4[C:20](=[CH:21][C:11]2=3)[CH2:19][CH2:18][O:17]4)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][C:23]1[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=1)[O:26][CH2:27][C:28]([OH:30])=[O:29]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 45280396HCID 45280396, compound

Product 1

HCID 45280397{3-[(2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-1'(2'H)-yl)methyl]phenoxy}acetic acidYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl {3-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]phenoxy}acetate (0.46 g, 0.98 mmol) in a mixture of tetrahydrofuran (30 mL) and water (15 mL) was added lithium hydroxide monohydrate (0.32 g, 2.3 mmol) at ambient temperature. The mixture was stirred at ambient temperature for 16 h. The mixture was concentrated in vacuo to a small volume, diluted with water (15 mL), washed with diethyl ether (60 mL), and acidified with 37% hydrochloric acid to pH 1. A white precipitate was formed. The mixture was extracted with ethyl acetate (3×60 mL). The combined organic solution was washed with water (30 mL), brine (50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford {3-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]phenoxy}acetic acid (0.41 g, 95%): mp 95-96° C.; 1H NMR (300 MHz, CDCl3) 7.33-7.14 (m, 3H), 7.07-6.97 (m, 2H), 6.92 (br s, 1H), 6.88-6.77 (m, 2H), 6.48 (s, 1H), 6.42 (s, 1H), 5.08-4.95 (m, 2H), 4.88-4.79 (m, 1H), 4.74-4.67 (m, 1H), 4.63 (s, 2H), 4.57-4.48 (m, 2H), 3.09-2.89 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 178.2, 172.6, 161.8, 161.3, 157.9, 141.9, 137.6, 132.6, 130.1, 128.8, 123.9, 123.6, 120.9, 120.0, 118.9, 113.9, 113.7, 113.7, 109.3, 93.2, 80.5, 72.4, 64.7, 57.8, 44.0, 29.0; MS (ES+) m/z 444.0 (M+1).

Workup

  1. concentrationThe mixture was concentrated in vacuo to a small volume
  2. additiondiluted with water (15 mL)
  3. washwashed with diethyl ether (60 mL)
  4. customA white precipitate was formed
  5. extractionThe mixture was extracted with ethyl acetate (3×60 mL)
  6. washThe combined organic solution was washed with water (30 mL), brine (50 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc67b00ad7314423a1e0fd416f129826
Source dataset
uspto-grants-2012_01
Patent number
US08101647B2

Reaction notes

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