Ethylene Glycol → 3-(4-cyanobenzoyl)indolizine

HRID 982691Notes

Reaction equation

HRID 982691 reaction equation
C([C:4]1[CH:5]=[C:6]([C:13](=[O:22])[C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)[N:7]2[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]2)(=O)C.C(O)CO.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C1C=CC=CC=1>[C:20]([C:17]1[CH:16]=[CH:15][C:14]([C:13]([C:6]2[N:7]3[C:12]([CH:11]=[CH:10][CH:9]=[CH:8]3)=[CH:4][CH:5]=2)=[O:22])=[CH:19][CH:18]=1)#[N:21]

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 22563203HCID 22563203, compound

Product 1

HCID 102639353-(4-cyanobenzoyl)indolizineYield 80%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of 1-acetyl-3-(4-cyanobenzoyl)indolizine (12) (1.56 grams, 5.69 mmol), ethylene glycol (1 mL), and p-toluenesulfonic acid (2.16 grams, 11.38 mmol) in benzene (150 mL) was refluxed for 3 hours. The reaction mixture was cooled to room temperature, neutralized with saturated sodium bicarbonate solution and extracted with ethyl acetate (3×50 mL). The combined layers were concentrated in vacuo. Purification by flash column chromatography (Rf 0.3, ethyl acetate in hexane) afforded 3-(4-cyanobenzoyl)indolizine (13) as a light yellow solid (1.12 grams, 80%). 1H NMR (CDCl3) δ 6.56 (d, J=4.8, 1H), 7.04 (t, J=6.9, 1H), 7.28 (m, 2H), 7.61 (d, J=9.0, 1H), 7.78 (m, 2H), 7.89 (m, 2H), 9.98 (d, J=7.2, 1H). ESMS calcd (C16H10N2O2): 246.1. found: 247.1 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. concentrationThe combined layers were concentrated in vacuo
  3. customPurification by flash column chromatography (Rf 0.3, ethyl acetate in hexane)

Sources & evidence

ORD record
ord-07127b7f93774cc3a447208ba6acc471
Source dataset
uspto-grants-2005_03
Patent number
US06861436B2

Reaction notes

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