Hydrochloric Acid → (2-Amino-5,6,7,8-tetrahydroquinolin-3-yl)(p-tolyl)methanone

HRID 2276347Notes

Reaction equation

HRID 2276347 reaction equation
[NH2:1][C:2]1[C:11]([C:12]#N)=[CH:10][C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1.[C:14]1([CH3:22])[CH:19]=[CH:18][C:17]([Mg]Br)=[CH:16][CH:15]=1.Cl.[OH-:24].[Na+]>O1CCCC1>[NH2:1][C:2]1[C:11]([C:12]([C:17]2[CH:18]=[CH:19][C:14]([CH3:22])=[CH:15][CH:16]=2)=[O:24])=[CH:10][C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 112290713-Quinolinecarbonitrile, 2-amino-5,6,7,8-tetrahydro-HCID 178418370HCID 178418370, compound

Product 1

HCID 69673592(2-Amino-5,6,7,8-tetrahydroquinolin-3-yl)(p-tolyl)methanoneYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-amino-5,6,7,8-tetrahydroquinoline-3-carbonitrile (1.2 g; 6.93 mmol) in dry tetrahydrofurane (70 mL) under nitrogen atmosphere was slowly added a solution of p-tolylmagnesium bromide (1M in THF) (35 mL; 35 mmol). The resulting solution was stirred at room temperature for 3 h and heated at 50° C. for 3 h. A solution of hydrochloric acid 3N (140 mL) was added to hydrolyse the intermediate imine and the reaction mixture was heated to reflux for 3 h. After cooling at 0° C., the reaction mixture was basified with a solution of sodium hydroxide 6N. The product was extracted with dichloromethane (200 mL) and the organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (10-100%) in dichloromethane as eluent furnished 1.51 g (82%) of (2-amino-5,6,7,8-tetrahydroquinolin-3-yl)(p-tolyl)methanone as a bright yellow solid. ESI/APCI(+): 267 (M+H).

Workup

  1. temperatureheated at 50° C. for 3 h
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for 3 h
  4. temperatureAfter cooling at 0° C.
  5. extractionThe product was extracted with dichloromethane (200 mL)
  6. dry with materialthe organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (10-100%) in dichloromethane as eluent

Sources & evidence

ORD record
ord-427dc043e86e40b9a7bf505702391fac
Source dataset
uspto-grants-2015_09
Patent number
US09132129B2

Reaction notes

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