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

HRID 875315Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 875315
[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].Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][CH:42]=2)=[CH:37][C:36]=1[Cl:51].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:40]=[CH:39][C:38]([C:41]2[CH:42]=[CH:43][C:44]([C:47]([F:48])([F:50])[F:49])=[CH:45][CH:46]=2)=[CH:37][C:36]=1[Cl:51])[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]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 86709811Ethyl 5-{(tert-butoxycarbonyl)[2-(2-hydroxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylateHCID 867098134-(Bromomethyl)-3-chloro-4'-(trifluoromethyl)biphenyl

Produkt 1

HCID 86709812Ethyl 5-{(tert-butoxycarbonyl)[2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

250 mg (0.57 mmol) of rac-ethyl 5-{(tert-butoxycarbonyl)[2-(2-hydroxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate (Example 10A), 277 mg (0.68 mmol) of 4-(bromomethyl)-3-chloro-4′-(trifluoromethyl)biphenyl and 118 mg (0.85 mmol) of potassium carbonate in 10 ml of acetonitrile were heated to 110° C. and stirred at this temperature for 4 h. 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). The product obtained in this manner was re-purified by preparative HPLC (mobile phase: methanol/water 9:1). This gave 182 mg (0.26 mmol, 45% of theory) of the target compound.

Aufarbeitung

  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)
  7. customThe product obtained in this manner
  8. customwas re-purified by preparative HPLC (mobile phase: methanol/water 9:1)

Quellen und Nachweise

ORD-Eintrag
ord-a6e89a4f18654cdfb4cc4c04e6a0c6cd
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08981104B2

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