Potassium Carbonate → Ethyl 5-[(tert-butoxycarbonyl)(2-{2-[(4-{2-[4-(trifluoromethyl)phenyl]ethyl}benzyl)oxy]phenyl}-ethyl)amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate

HRID 875345Notes

Reaction equation

HRID 875345 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[OH:32])[CH:9]1[CH2:18][CH2:17][CH2:16][C:15]2[N:14]=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:12]=[CH:11][C:10]1=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][CH:44]=2)=[CH:37][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH2:34][C:35]1[CH:36]=[CH:37][C:38]([CH2:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([C:49]([F:50])([F:51])[F:52])=[CH:45][CH:44]=2)=[CH:39][CH:40]=1)[CH:9]1[CH2:18][CH2:17][CH2:16][C:15]2[N:14]=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:12]=[CH:11][C:10]1=2)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 207707551-(Chloromethyl)-4-{2-[4-(trifluoromethyl)phenyl]ethyl}benzeneHCID 86709811Ethyl 5-{(tert-butoxycarbonyl)[2-(2-hydroxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

Product 1

HCID 86709835Ethyl 5-[(tert-butoxycarbonyl)(2-{2-[(4-{2-[4-(trifluoromethyl)phenyl]ethyl}benzyl)oxy]phenyl}-ethyl)amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1 g (2.27 mmol) of ethyl 5-{(tert-butoxycarbonyl)[2-(2-hydroxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate (Enantiomer 2, Example 69A), 746 mg (2.50 mmol) of 1-(chloromethyl)-4-{2-[4-(trifluoromethyl)phenyl]ethyl}benzene and 784 mg (5.68 mmol) of potassium carbonate in 25 ml of acetonitrile were heated to 110° C. and stirred at this temperature overnight. After cooling, the reaction mixture was filtered, the filter cake was washed repeatedly with acetonitrile and the combined filtrates were concentrated to dryness on a rotary evaporator. The residue obtained was purified chromatographically on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1→10:1). This gave 1110 mg (1.48 mmol, 65% of theory) of the target compound.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction mixture was filtered
  3. washthe filter cake was washed repeatedly with acetonitrile
  4. concentrationthe combined filtrates were concentrated to dryness on a rotary evaporator
  5. customThe residue obtained
  6. customwas purified chromatographically on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1→10:1)

Sources & evidence

ORD record
ord-235c8561b66a4f3393b7dc645932f67f
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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