Potassium Hydroxide → 7-((5-Methyl-1H-imidazol-4-yl)methyl)-5,6,7,8-tetrahydroquinoline

HRID 252083Notes

Reaction equation

HRID 252083 reaction equation
[CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][CH:8]1[C:17](=O)[C:16]2[N:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:10][CH2:9]1.[OH-].[K+].O.NN>C(O)CO.O>[CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][CH:8]1[CH2:17][C:16]2[N:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:10][CH2:9]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 593166327-((5-Methyl-1H-imidazol-4-yl)methyl)-6,7-dihydroquinolin-8(5H)-one

Product 1

HCID 248603017-((5-Methyl-1H-imidazol-4-yl)methyl)-5,6,7,8-tetrahydroquinolineYield 70%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (5) (0.83 g, 344 mmol), potassium hydroxide (0.782 g, 13.9 mmol), and hydrazine hydrate (0.77 mL, 24.7 mmol) in ethylene glycol (20 mL) was heated at 120° C. in an apparatus fitted with a Dean Stark trap for 1 h, and at 180° C. for 4 hours. The reaction was cooled to rt, and diluted with water. The aqueous medium was extracted three times with chloroform/isopropanol (3:1, 200 mL). The pooled organic layers were dried over magnesium sulfate. The mixture was filtered and the solvents were removed under vacuum. The residue was purified by chromatography on silica gel with 2 to 3% ammonia saturated methanol in dichloromethane to give 7-(5-methyl-1H-imidazol-4-ylmethyl)-5,6,7,8-tetrahydro-quinoline (6) as a foam (0.544 g, 2.40 mmol, 70% yield). 1H NMR (300 MHz, CDCl3): δ 8.30 (d, J=3.90 Hz, 1H), 7.43 (s, 1H), 7.37 (d, J=7.50 Hz, 1H), 7.03 (dd, J=7.50, 4.80 Hz, 1H), 2.99-2.91 (m, 1H), 2.84-2.76 (m, 2H), 2.70-2.50 (m, 3H), 2.24-2.14 (m, 1H), 2.15 (s, 3H), 2.04-1.96 (m, 1H), 1.54-1.40 (m, 1H).

Workup

  1. customfitted with a Dean Stark trap for 1 h
  2. temperatureThe reaction was cooled to rt
  3. extractionThe aqueous medium was extracted three times with chloroform/isopropanol (3:1, 200 mL)
  4. dry with materialThe pooled organic layers were dried over magnesium sulfate
  5. filtrationThe mixture was filtered
  6. customthe solvents were removed under vacuum
  7. customThe residue was purified by chromatography on silica gel with 2 to 3% ammonia saturated methanol in dichloromethane

Sources & evidence

ORD record
ord-5984c4a545b848b2b0eb9431958b4496
Source dataset
uspto-grants-2011_01
Patent number
US07868020B2

Reaction notes

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