Sodium Hydroxide → 3-(2-Phenylethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

HRID 2169014Notes

Reaction equation

HRID 2169014 reaction equation
[C:1]1([CH2:7][CH2:8][C:9]2[N:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:18]([O:20]CC)=[O:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>C(O)C>[C:1]1([CH2:7][CH2:8][C:9]2[N:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:18]([OH:20])=[O:19])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58355694Ethyl 3-(2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxylate

Product 1

HCID 673212403-(2-Phenylethyl)imidazo[1,2-a]pyridine-2-carboxylic acidYield 128.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 3-(2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxylate (883 mg) was dissolved in ethanol (50 ml), 2N aqueous sodium hydroxide solution (3 ml) was added, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated under reduced pressure, neutralized with 1N hydrochloric acid, subjected to DIAION HP-(manufactured by Mitsubishi Chemical), and washed with water. The fraction eluted with acetone was concentrated under reduced pressure to give 3-(2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxylic acid (1.03 g). The obtained 3-(2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxylic acid (341 mg), tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (370 mg) and N,N-diisopropylethylamine (862 μl) were dissolved in acetonitrile (20 ml), chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (561 mg) was added and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated, and the residue was diluted with aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (9:1) was concentrated under reduced pressure to give the object product (522 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washwashed with water
  3. washThe fraction eluted with acetone
  4. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-45a8ecfd8faf49f69e4b7d9b77313d65
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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