1-(Phenylmethyl)-1H-indole-3-carboxylic acid

General procedure: In a 50 mL autoclave equipped with a glass inner tube and a magnetic stirring bar were charged indole 1a (d 1.05; 125 mL, 1.00 mmol), Me2AlCl (1.0 M solution in hexane; 1.0 mL, 1.0 mmol), toluene (1.0 mL) under nitrogen atmosphere, and the apparatus was purged with CO2 by repeated pressurization and subsequent expansion, the final pressure being adjusted to 3.0 MPa. After the mixture was stirred at 80 °C for 3 h, the reactor was allowed to cool to room temperature and depressurized. The reaction mixture was quenched with 2 M HCl and the aqueous layer was extracted with ethyl acetate. The combined organic layer was extracted with 0.5M Na2CO3 and the extract was acidified by the addition of concentrated HCl to liberate the free carboxylic acid, which was extracted with ethyl acetate. The extract was dried over MgSO4 and evaporated to leave a residue, which was purified by column chromatography with chloroform-ethyl acetate (1:1) as an eluent to give acid 2a as crystals (168 mg, 96percent). The carboxylation of other indoles was conducted by a similar procedure. The crude product was routinely purified by column chromatography using chloroform-ethyl acetate (1:1) or chloroform-ethyl acetate (1:1) containing 1percent (v/v) of acetic acid as an eluent. See Tables 1 and 2 for the reaction conditions and product yields.(Step 2) 1-benzyl-1H-indole-3-carboxylic acid 1-benzyl-1H-indole-3-carboxylic acid; To a stirred solution of 0.50 g (3.10 mmol) 1H-indole-3-carboxylic acid in 5 ml DMF was added 0.27 g (6.75 mmol) of NaH (60percent in oil). The mixture was stirred at RT for 30 min. and then 0.39 ml (3.28 mmol) of benzyl bromid was added. The mixture was stirred an additional hour and then poured onto water and extracted with ethyl acetate. The combined organic phases were dried over Na1 H-indole-3-carboxylic acid (2.5 g)In DMF (25 mL) was added 60percent sodium hydride (1.4 g)After stirring at room temperature for 40 minutes, Benzyl bromide 2.0 mL) was added dropwise, And the mixture was stirred at room temperature for 19 hours. Water (10 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained aqueous layer was made acidic, extracted with ethyl acetate, and washed with saturated brine.The organic layer was dried over sodium sulfate, Crystals obtained by distilling off the solvent under reduced pressure were crystallized fromWashed with ethanol to obtain 2.8 g (yield 72percent) of 1-benzyl-1 H-indole-3-carboxylic acid.

Reactant for preparation of:• ;Indoleacetic acid analogs as differentiation-inducing and antiproliferative agents for human myeloblastoma cells1• ;Indole-carboxamide derivatives as inhibitors of lipid peroxidation and superoxide anion formation2• ;Indole carboxamides as hyaluronidase inhibitors3• ;Fuconojirimycin derivatives as inhibitors of α-fucosidases4• ;Indole-2 and 3-carboxamides as selective cyclooxygenase-2 inhibitors5• ;Indole amides as antihistaminic agents6

Molecular Weight:251.28
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:251.094628657
Monoisotopic Mass:251.094628657
Topological Polar Surface Area:42.2
Heavy Atom Count:19
Complexity:325
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes