Sodium Carbonate → Ethyl 5-([2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]{2-[4-(methoxycarbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate

HRID 875326Notes

Reaction equation

HRID 875326 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:34]2[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][CH2:17][NH:18][CH:19]1[CH2:28][CH2:27][CH2:26][C:25]2[N:24]=[C:23]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:22]=[CH:21][C:20]1=2.I[CH2:45][CH2:46][C:47]1[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][CH:48]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:34]2[CH:35]=[CH:36][C:37]([C:40]([F:43])([F:41])[F:42])=[CH:38][CH:39]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][CH2:17][N:18]([CH2:45][CH2:46][C:47]1[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][CH:48]=1)[CH:19]1[CH2:28][CH2:27][CH2:26][C:25]2[N:24]=[C:23]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:22]=[CH:21][C:20]1=2

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 22639144Methyl 4-(2-iodoethyl)benzoate2×HCID 86709815Ethyl 5-{[2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

Product 1

HCID 86709816Ethyl 5-([2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]{2-[4-(methoxycarbonyl)phenyl]ethyl}amino)-5,6,7,8-tetrahydroquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 69 g (111.24 mmol) of ethyl 5-{[2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate (Enantiomer 2, Example 86A), 129 g (444.98 mmol) of methyl 4-(2-iodoethyl)benzoate and 17.68 g (166.87 mmol) of anhydrous sodium carbonate in 1500 ml of dry acetonitrile was stirred at a bath temperature of 110° C. overnight. A further 65.54 g of methyl 4-(2-iodoethyl)benzoate and 23.06 g (166.87 mmol) of powdered potassium carbonate were then added, and the mixture was heated under reflux for another 48 h. After cooling of the reaction mixture, the inorganic salts were filtered off and the filtrate obtained was evaporated to dryness. The resulting residue was taken up in ethyl acetate, washed twice with 10% strength aqueous sodium chloride solution, dried over magnesium sulphate, filtered and then once more evaporated to dryness. The residue obtained was purified chromatographically on silica gel (3 kg) (mobile phase: petroleum ether/ethyl acetate 8:2→7:3). This gave 42 g (54.45 mmol, 49% of theory) of the target compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for another 48 h
  3. temperatureAfter cooling of the reaction mixture
  4. filtrationthe inorganic salts were filtered off
  5. customthe filtrate obtained
  6. customwas evaporated to dryness
  7. washwashed twice with 10% strength aqueous sodium chloride solution
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. customonce more evaporated to dryness
  11. customThe residue obtained
  12. customwas purified chromatographically on silica gel (3 kg) (mobile phase: petroleum ether/ethyl acetate 8:2→7:3)

Sources & evidence

ORD record
ord-62835da29599473abdcf2dea7066489b
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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