Hydrochloric Acid → 3-(4-Phenylbenzoyl)quinuclidine hydrogen chloride

HRID 976287

Reaktionsgleichung

Reaktionsgleichung von HRID 976287
C([Li])(CC)C.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.[C:19]([CH:21]1[CH:26]2[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]2)[CH2:22]1)#N.[ClH:29].[O:30]1CCCC1>CCCCCC>[ClH:29].[C:13]1([C:10]2[CH:11]=[CH:12][C:7]([C:19]([CH:21]3[CH:26]4[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]4)[CH2:22]3)=[O:30])=[CH:8][CH:9]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 71014-BromobiphenylHCID 8028Tetrahydrofuran2×HCID 1428651-Azabicyclo(2.2.2)octane-3-carbonitrileHCID 178418400CID 53628100

Produkt 1

HCID 677116723-(4-Phenylbenzoyl)quinuclidine hydrogen chloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A solution of sec-butyl lithium in hexane (1.1M, 67.38 ml) was added to a solution of 4-bromobiphenyl (14.38 g) in dry tetrahydrofuran (128 ml) over a period of 1.5 hours under an atmosphere of argon at -78° C. The reaction mixture was stirred for 30 minutes at -78° C. A solution of 3-cyanoquinuclidine (5.6 g) in dry tetrahydrofuran was added to the reaction mixture whilst maintaining the temperature at -78° C. The reaction mixture was stirred for a further period of 16 hours during which period the reaction mixture was allowed to warm to ambient temperature. 2M aqueous hydrogen chloride solution (50 ml) was added to the reaction mixture and the mixture was stirred for 1 hour. The aqueous phase was separated, washed with diethyl ether, basified with dilute aqueous sodium hydroxide solution and extracted with ethyl acetate. The ethyl acetate extract was dried (MgSO4) and evaporated to give a residue which was purified by flash column chromatography on silica gel using a 95:5 (v/v) mixture of methanol/ammonia (density 0.88 g/cm3) as eluant. The residue was dissolved in ethanol and acidified with a saturated solution of ethanolic hydrogen chloride. The mixture was evaporated to dryness and hexane was added to give 3-(4-phenylbenzoyl)quinuclidine hydrogen chloride as a solid (970 mg), m.p. 255.6° C.; microanalysis, found: C, 71.4; H, 6.7; N, 4.4; Cl, 9.8%; C20H21NO. HCl 1/2 H2O. requires: C, 71.34; H, 6.8; N, 4.2; Cl, 10.5%; NMR (CDCl3): 1.7-1.85 (2H, m), 2.0-2.2 (2H, m), 2.2-2.45 (1H, m), 2.45-2.6 (1H, m), 3.2-3.5 (3H, m), 3.5-3.7 (2H, m), 3.9-4.2 (2H, m), 7.35-7.55 (3H, m), 7.55-7.65 (2H, m), 7.65-7.75 (2H, d), 8.0-8.1 (2H, d) and 12.26 (1H, s).

Aufarbeitung

  1. temperaturewhilst maintaining the temperature at -78° C
  2. stirringThe reaction mixture was stirred for a further period of 16 hours during which period the reaction mixture
  3. temperatureto warm to ambient temperature
  4. stirringthe mixture was stirred for 1 hour
  5. customThe aqueous phase was separated
  6. washwashed with diethyl ether
  7. extractionextracted with ethyl acetate
  8. extractionThe ethyl acetate extract
  9. dry with materialwas dried (MgSO4)
  10. customevaporated
  11. customto give a residue which
  12. customwas purified by flash column chromatography on silica gel using
  13. additiona 95:5 (v/v) mixture of methanol/ammonia (density 0.88 g/cm3) as eluant
  14. dissolutionThe residue was dissolved in ethanol
  15. customThe mixture was evaporated to dryness and hexane
  16. additionwas added

Quellen und Nachweise

ORD-Eintrag
ord-64c8b113b20d4b48929115bbe92d3b1b
Quelldatensatz
uspto-grants-1997_03
Patentnummer
US05612352

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