Sodium Carbonate → rac-Ethyl 5-[(2-{2-[(4-tert-butylbenzyl)oxy]phenyl}ethyl) {2-[4-(methoxycarbonyl)phenyl]ethyl}-amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate

HRID 875318Notes

Reaction equation

HRID 875318 reaction equation
Cl[CH2:2][CH2:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl.Cl.[C:22]([C:26]1[CH:57]=[CH:56][C:29]([CH2:30][O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[CH2:38][CH2:39][NH:40][CH:41]2[CH2:50][CH2:49][CH2:48][C:47]3[N:46]=[C:45]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH:44]=[CH:43][C:42]2=3)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23].ICCC1C=CC(C(OC)=O)=CC=1>C(#N)C>[C:22]([C:26]1[CH:27]=[CH:28][C:29]([CH2:30][O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[CH2:38][CH2:39][N:40]([CH2:2][CH2:3][C:4]2[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=2)[CH:41]2[CH2:50][CH2:49][CH2:48][C:47]3[N:46]=[C:45]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH:44]=[CH:43][C:42]2=3)=[CH:56][CH:57]=1)([CH3:24])([CH3:23])[CH3:25]

Participants

6

Reactant 4

HCID 10340Sodium Carbonate2×HCID 22098587Methyl 4-(2-chloroethyl)benzoate5×HCID 22639144Methyl 4-(2-iodoethyl)benzoateHCID 89940797Ethyl 5-[(2-{2-[(4-tert-butylbenzyl)oxy]phenyl}ethyl)amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate dihydrochloride

Product 1

HCID 89941256rac-Ethyl 5-[(2-{2-[(4-tert-butylbenzyl)oxy]phenyl}ethyl) {2-[4-(methoxycarbonyl)phenyl]ethyl}-amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

129 mg (0.65 mmol) of methyl 4-(2-chloroethyl)benzoate and 91 mg (0.86 mmol) of anhydrous sodium carbonate were added to a solution of 210 mg (0.43 mmol) of ethyl 5-[(2-{2-[(4-tert-butylbenzyl)oxy]phenyl}ethyl)amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate dihydrochloride in 4 ml of dry acetonitrile, and the mixture was initially heated under reflux for 4 hours. A further 0.1 ml of methyl 4-(2-chloroethyl)benzoate was then added, and the mixture was stirred under reflux for 4 hours. Another 0.1 ml of methyl 4-(2-chloroethyl)benzoate was metered in, and the mixture was then heated under reflux overnight. Subsequently, another 0.1 ml of methyl 4-(2-chlor-oethyl)benzoate and 100 mg of anhydrous sodium carbonate were added, and the mixture was stirred under reflux for a further 5 hours. Finally, another 0.1 ml of methyl 4-(2-chloroethyl)-benzoate and 0.2 ml of methyl 4-(2-iodoethyl)benzoate were added, and the reaction mixture was stirred under reflux for 2 days. The reaction was then concentrated to dryness. The residue obtained was purified by preparative HPLC. This gave 38 mg (0.06 mmol, content 92%, 14% of theory) of the title compound as a colourless oil.

Workup

  1. temperaturethe mixture was initially heated
  2. temperatureunder reflux for 4 hours
  3. temperatureunder reflux for 4 hours
  4. temperaturewas then heated
  5. temperatureunder reflux overnight
  6. stirringthe mixture was stirred
  7. temperatureunder reflux for a further 5 hours
  8. stirringthe reaction mixture was stirred
  9. temperatureunder reflux for 2 days
  10. concentrationThe reaction was then concentrated to dryness
  11. customThe residue obtained
  12. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-c971c0d010ba439f811c4cabc13d65e6
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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