Lithium hydroxide, monohydrate → 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid

HRID 42519Notes

Reaction equation

HRID 42519 reaction equation
C[O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([CH:16]([CH3:18])[CH3:17])[C:10]=2[CH:11]=[C:12]([O:14][CH3:15])[CH:13]=1)=[O:4].O[Li].O>C1COCC1.O>[CH:16]([N:9]1[C:10]2[CH:11]=[C:12]([O:14][CH3:15])[CH:13]=[C:5]([C:3]([OH:4])=[O:2])[C:6]=2[CH:7]=[CH:8]1)([CH3:18])[CH3:17]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 674645681-isopropyl-6-methoxy-1H-indole-4-carboxylic acid methyl ester

Product 1

HCID 674656271-isopropyl-6-methoxy-1H-indole-4-carboxylic acidYield 69.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid methyl ester (320 mg, 1.29 mmol) in THF (2 mL) was added LiOH.H2O (160 mg, 3.88 mmol) in water (2 mL) at room temperature and heated at reflux for 2 h. The THF was removed under reduced pressure and the resulting aqueous layer was acidified with 1 N HCl (pH ˜6) and extracted with ethyl acetate (2×5 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated to afford 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid (210 mg). 1H NMR (400 MHz, DMSO-d6): δ 1.42 (d, 6H), 3.88 (s, 3H), 4.85 (m, 1H), 6.81 (d, J=2.8 Hz, 1H), 7.26 (s, 2H), 7.45 (s, 1H), 12.68 (s, 1H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 h
  3. customThe THF was removed under reduced pressure
  4. extractionextracted with ethyl acetate (2×5 mL)
  5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a8bf7f95cf3b48b8988b36f3d5d9375b
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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