Methanol → 5-(2-hydroxyethoxy)-1H-indole-2-carboxylic acid

HRID 1874948Notes

Reaction equation

HRID 1874948 reaction equation
CO.[CH3:3][C:4]([Si:7]([CH3:34])([CH3:33])[O:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17](C(OCCC(C)(C)C)=O)[C:16]([C:30]([O-:32])=[O:31])=[CH:15]2)([CH3:6])[CH3:5].[Li+].[OH-]>C1COCC1>[OH:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16]([C:30]([OH:32])=[O:31])=[CH:15]2.[CH3:6][C:4]([Si:7]([CH3:34])([CH3:33])[O:8][CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16]([C:30]([OH:32])=[O:31])=[CH:15]2)([CH3:3])[CH3:5]

Participants

6

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 86761647HCID 86761647, compound

Product 2

HCID 184556225-(2-hydroxyethoxy)-1H-indole-2-carboxylic acidYield 16%HCID 68485440HCID 68485440, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A methanol solution of 1-(1,1-dimethylethyl)2-ethyl 5-[(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)oxy]-1H-indole-1,2-dicarboxylate (0.200 g, 0.431 mmol) was treated with 1 N LiOH (4 mL). A precipitate formed and THF was added to redissolve the material. The reaction was heated to 70° C. until the starting material was consumed, partitioned between EtOAc and water and the layers separated. The basic aqueous layer was acidified with conc. HCl and extracted with EtOAc. Purification was accomplished by silica gel column chromatography (0-100% EtOAc/hexanes, striped with MeOH) to afford the title compound (0.015 g, 16%) and 5-[(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)oxy]-1H-indole-2-carboxylic acid (0.0114 g, 7%) 1H NMR (400 MHz, Acetone-d6) δ ppm 10.73 (br. s., 1H), 7.43 (d, 1H), 7.15 (d, 1H), 7.10 (d, 1H), 6.96 (dd, 1H), 4.07 (t, 2H), 3.88 (t, 2H).

Workup

  1. customA precipitate formed
  2. dissolutionto redissolve the material
  3. customwas consumed
  4. custompartitioned between EtOAc and water
  5. customthe layers separated
  6. extractionextracted with EtOAc
  7. customPurification

Sources & evidence

ORD record
ord-45ac2a52a60e41f3bce3c4b49340bdf9
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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