Water → HCID 131711941, Verbindung

HRID 443388

Reaktionsgleichung

Reaktionsgleichung von HRID 443388
[OH-].[Na+].O.[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[CH:12]([OH:19])[CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1.Cl.[Cl:21][N:22]1[C:31]2[CH:30]=[C:29]3[O:32][CH2:33][O:34][C:28]3=[CH:27][C:26]=2[CH:25]=[C:24](CCl)[CH2:23]1.O1CCC[CH2:38]1>[Cl-].C([N+](C)(C)C)C1C=CC=CC=1>[ClH:4].[Cl:21][N:22]1[C:31]2[CH:30]=[C:29]3[O:32][CH2:33][O:34][C:28]3=[CH:27][C:26]=2[CH:25]=[CH:24][CH:23]1[CH2:38][O:19][CH:12]([C:6]1[CH:7]=[CH:8][C:9]([Cl:11])=[CH:10][C:5]=1[Cl:4])[CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1

Komponenten

7

Edukt 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 32238(+-)-alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanolHCID 131711942HCID 131711942, Verbindung

Produkt 1

HCID 131711941HCID 131711941, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 5963Benzyltrimethylammonium chlorideKatalysator

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

In a three-necked flask, fitted with stirrer, reflux condenser and gas inlet tube, are introduced 17.0 g of sodium hydroxide (0.425 mol) and 16 ml of water. While passing nitrogen through the flask, the solution is cooled to 45° C. and then are added 4.5 g of 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol (0.0174 mol) [prepared according to J. Med. Chem., Vol. 12, 784 (1969)], 0.3 g of benzyltrimethylammonium chloride and 30 ml of of tetrahydrofuran. To the mixture, which is warmed to 50° C., 5.08 g of 5-chloro-7-chloromethyl-1,3-dioxolo[4,5-g]quinoline, hydrochloride (0.0174 mol) are added portionwise. The mixture is stirred vigorously for 3 hours at 60° C. using a water bath. Then the warm mixture is transferred into a separating funnel, the lower aqueous sodium hydroxide is extracted with 15 ml of tetrahydrofuran. The combined tetrahydrofuran layers are dried by means of sodium sulfate, charcoaled and removed to a volume of about 20 ml. Addition of 250 ml of ether precipitates an oily side product (1.6 g). To the solution of the free base are added dropwise ethereal hydrochloric acid. Initially the hydrochloride of 5-chloro-6-[[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]methyl]-1,3-dioxolo-[4,5-g]quinoline precipitates in oily form which, after standing overnight, becomes crystalline (6.6 g; m.p. 237°-238° C. dec.). After trituration with a small amount of methanol, the dihydrochloride is filtered off, washed with cooled methanol and dried at 70° C. Yield 5.5 g (58%), m.p. 242°-243° C. dec.

Aufarbeitung

  1. customIn a three-necked flask, fitted with stirrer
  2. temperaturereflux condenser and gas inlet tube
  3. temperatureTo the mixture, which is warmed to 50° C.
  4. customThen the warm mixture is transferred into a separating funnel
  5. extractionthe lower aqueous sodium hydroxide is extracted with 15 ml of tetrahydrofuran
  6. dry with materialThe combined tetrahydrofuran layers are dried by means of sodium sulfate
  7. customremoved to a volume of about 20 ml
  8. additionAddition of 250 ml of ether
  9. customprecipitates an oily side product (1.6 g)
  10. additionTo the solution of the free base are added dropwise ethereal hydrochloric acid
  11. customInitially the hydrochloride of 5-chloro-6-[[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]methyl]-1,3-dioxolo-[4,5-g]quinoline precipitates in oily form which
  12. waitafter standing overnight
  13. filtrationAfter trituration with a small amount of methanol, the dihydrochloride is filtered off
  14. washwashed with cooled methanol
  15. customdried at 70° C

Quellen und Nachweise

ORD-Eintrag
ord-e01df1fc89d9491ebfaf9f5eadb4d807
Quelldatensatz
uspto-grants-1981_04
Patentnummer
US04260616

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