Potassium Iodide → Ethyl 5-{(2-cyano-5,6,7,8-tetrahydroquinolin-5-yl)[2-(2-methoxyphenyl)ethyl]amino}pentanoate

HRID 875305Notes

Reaction equation

HRID 875305 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[I-].[K+].C(=O)([O-])[O-].[Na+].[Na+].[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH2:27][CH2:28][NH:29][CH:30]1[CH2:39][CH2:38][CH2:37][C:36]2[N:35]=[C:34]([C:40]#[N:41])[CH:33]=[CH:32][C:31]1=2>C(#N)C.C(OCC)(=O)C>[C:40]([C:34]1[CH:33]=[CH:32][C:31]2[CH:30]([N:29]([CH2:28][CH2:27][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[O:20][CH3:19])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:39][CH2:38][CH2:37][C:36]=2[N:35]=1)#[N:41]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 84580Ethyl 5-bromovalerateHCID 899408535,6,7,8-Tetrahydro-5-[[2-(2-methoxyphenyl)ethyl]amino]-2-quinolinecarbonitrile

Product 1

HCID 89940888Ethyl 5-{(2-cyano-5,6,7,8-tetrahydroquinolin-5-yl)[2-(2-methoxyphenyl)ethyl]amino}pentanoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

17.07 ml (0.11 mol) of ethyl 5-bromopentanoate, 8.43 g (0.05 mol) of potassium iodide and 22.61 g (0.21 mol) of anhydrous sodium carbonate were added to a solution of 31.22 g (0.10 mol) of 5-{[2-(2-methoxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carbonitrile in 300 ml of dry acetonitrile, and the mixture was heated under reflux for 4 days. The reaction was then concentrated to a volume of about 50 ml on a rotary evaporator. The solution obtained was taken up in 250 ml of ethyl acetate and 400 ml of saturated aqueous sodium chloride solution, and the organic phase was then removed. The aqueous phase was extracted twice with in each case 150 ml of ethyl acetate. The combined organic phases were dried over sodium sulphate, filtered and concentrated to dryness. The residue obtained was applied to 25 g of silica gel and purified by column chromatography on silica gel (80 g cartridge; flow rate: 60 ml/min; mobile phase: petroleum ether/ethyl acetate 95:5→80:20 over 30 min). This gave 28.89 g (0.05 mol, content 80%, 52% of theory) of the target compound as an orange oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 days
  3. concentrationThe reaction was then concentrated to a volume of about 50 ml on a rotary evaporator
  4. customThe solution obtained
  5. custom400 ml of saturated aqueous sodium chloride solution, and the organic phase was then removed
  6. extractionThe aqueous phase was extracted twice with in each case 150 ml of ethyl acetate
  7. dry with materialThe combined organic phases were dried over sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue obtained
  11. custompurified by column chromatography on silica gel (80 g cartridge; flow rate: 60 ml/min; mobile phase: petroleum ether/ethyl acetate 95:5→80:20 over 30 min)

Sources & evidence

ORD record
ord-e6ab819c2b9a4210a6c854ff3f9e1dfb
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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