Water → 2-[(2-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)methyl]pyridine-3-carboxylic acid

HRID 2385457Notes

Reaction equation

HRID 2385457 reaction equation
O=[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[C:29]([C:30]([O:32]CC)=[O:31])=[CH:28][CH:27]=[CH:26][N:25]=1.[OH-].[Li+].[O:37]1CCCC1.O>CO>[O:37]=[C:18]1[O:17][C:16]2[CH:21]=[C:22]3[C:10]4([C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[N:3]([CH2:23][C:24]5[C:29]([C:30]([OH:32])=[O:31])=[CH:28][CH:27]=[CH:26][N:25]=5)[CH2:2]4)[CH2:11][O:12][C:13]3=[CH:14][C:15]=2[O:20][CH2:19]1

Participants

6

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 59352395ethyl 2-[(2'-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)methyl]pyridine-3-carboxylate

Product 1

HCID 685996942-[(2-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-1'(2'H)-yl)methyl]pyridine-3-carboxylic acidYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 250 mL round-bottom flask was charged with ethyl 2-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]pyridine-3-carboxylate (2.3 g, 5.0 mmol), lithium hydroxide (0.48 g, 20.0 mmol), tetrahydrofuran (30.mL), water (50.mL) and methanol (30 mL). The reaction mixture was stirred under nitrogen at reflux for 5 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was taken up in water (100 mL) and acidified to pH 1 by the addition of 10 M hydrochloric acid, causing a precipitate to be deposited. The solid was collected by filtration, washed with water and recrystallized from ethanol (50 mL) to afford 2-[(2-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]pyridine-3-carboxylic acid (1.96 g, 91%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ8.57-8.45 (m, 1H), 8.33-8.26 (m, 1H), 7.42 (dd, J=7.82, 4.77 Hz, 1H), 7.21-6.83 (m, 4H), 6.49-6.44 (m, 2H), 5.39 (ABq, 2H), 4.72 (ABq, 2H), 4.24-4.00 (m, 4H).

Workup

  1. temperatureat reflux for 5 h
  2. concentrationconcentrated in vacuo
  3. additionacidified to pH 1 by the addition of 10 M hydrochloric acid
  4. filtrationThe solid was collected by filtration
  5. washwashed with water
  6. customrecrystallized from ethanol (50 mL)

Sources & evidence

ORD record
ord-46f02d2d714f4274b1c881eac2045f49
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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