Lithium hydroxide, monohydrate → 2-(3-(Benzo[d][1,3]dioxol-5-yl)-2-oxo-1-pentylindolin-3-yl)acetic acid

HRID 1259565Notes

Reaction equation

HRID 1259565 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([CH2:25][C:26]([O:28]C)=[O:27])[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:11]3=[O:24])=[CH:9][C:4]=2[O:3][CH2:2]1.O.[OH-].[Li+]>C1COCC1.O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([CH2:25][C:26]([OH:28])=[O:27])[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:11]3=[O:24])=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 12003986HCID 12003986, compound

Product 1

HCID 545864982-(3-(Benzo[d][1,3]dioxol-5-yl)-2-oxo-1-pentylindolin-3-yl)acetic acidYield 88%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of methyl [3-(1,3-benzodioxol-5-yl)-2-oxo-1-pentyl-2,3-dihydro-1H-indol-3-yl]acetate (5.90 g, 15.0 mmol) in THF/water (2/1 v/v, 120 mL) was added lithium hydroxide monohydrate (1.26 g, 28.0 mmol). The mixture was stirred at ambient temperature overnight. Most THF was removed under vacuum and water (150 mL) was added. The solution was extracted with ethyl acetate/hexanes (1/3 v/v, 50.0 mL). The water layer was acidified with 1 N HCl solution until the pH value reached 2 and extracted with ethyl acetate (200 mL). The organic layer was washed with water, dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness to afford the title compound (5.00 g, 88%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.29 (td, 1H), 7.21 (dd, 1H), 7.05 (td, 1H), 6.87 (d, 1H), 6.76 (d, 1H), 6.72-6.64 (m, 2H), 5.90-5.86 (m, 2H), 3.65 (t, 2H), 3.43 (d, 1H), 3.11 (d, 1H), 1.70-1.55 (m, 2H), 1.36-1.22 (m, 4H), 0.85 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 178.2, 174.0, 148.0, 147.1, 143.4, 132.6, 131.4, 128.7, 124.4, 122.7, 119.8, 108.9, 108.2, 107.2, 101.2, 52.6, 41.5, 40.4, 29.0, 26.6, 22.3, 14.0; MS (ES+) m/z 404.0 (M+23), 382.0 (M+1).

Workup

  1. customMost THF was removed under vacuum and water (150 mL)
  2. additionwas added
  3. extractionThe solution was extracted with ethyl acetate/hexanes (1/3 v/v, 50.0 mL)
  4. extractionextracted with ethyl acetate (200 mL)
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-ca15f26eae86412286b2bc7617e461c3
Source dataset
uspto-grants-2013_06
Patent number
US08466188B2

Reaction notes

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