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

HRID 875339Notes

Reaction equation

HRID 875339 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[OH:33])[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[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][CH2:43][C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)=[CH:38][CH:37]=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]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[O:33][CH2:35][C:36]1[CH:37]=[CH:38][C:39]([CH2:42][CH2:43][C:44]2[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=2)=[CH:40][CH:41]=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 220150131-(Chloromethyl)-4-[2-(4-fluorophenyl)ethyl]benzeneHCID 89950552Rac-ethyl 5-{(tert-butoxycarbonyl)[2-(5-fluoro-2-hydroxyphenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

Product 1

HCID 86709832Ethyl 5-[(tert-butoxycarbonyl){2-[5-fluoro-2-({4-[2-(4-fluorophenyl)ethyl]benzyl}oxy)phenyl]-ethyl}amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

10 g (21.81 mmol) of rac-ethyl 5-{(tert-butoxycarbonyl)[2-(5-fluoro-2-hydroxyphenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate (Example 106A), 5.98 g (23.99 mmol) of 1-(chloromethyl)-4-[2-(4-fluorophenyl)ethyl]benzene and 4.52 g (32.71 mmol) of potassium carbonate in 240 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 10:1→4:1). This gave 14.11 g (21.03 mmol, 96% 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 10:1→4:1)

Sources & evidence

ORD record
ord-924a8406c7b6461395d818cee031450a
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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