p-Bromochlorobenzene → 3-(4-Chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol

HRID 1266994

Reaktionsgleichung

Reaktionsgleichung von HRID 1266994
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1.[CH3:14][N:15]1[CH:20]2[CH2:21][CH2:22][CH:16]1[CH2:17][C:18](=[O:23])[CH2:19]2>C(OCC)C>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C:18]2([OH:23])[CH2:19][CH:20]3[N:15]([CH3:14])[CH:16]([CH2:22][CH2:21]3)[CH2:17]2)=[CH:8][CH:9]=1

Komponenten

5

Edukt 3

HCID 7806p-BromochlorobenzeneHCID 79038Npc164516HCID 178418339Butyllithium

Produkt 1

HCID 4344883-(4-Chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-olAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel3×

Versuchsvorschrift

2.5 M n-butyl lithium (17.96 mL, 40.90 mmol) was added to -70 ° C diethyl ether (35 mL) and 4-bromochlorobenzene (9.03 g, 47.15 mmol) in diethyl ether (20mL) was added dropwise over 20 minutes. The mixture was stirred in the cold for 20 minutes then 8-Methyl-8-aza-bicyclo[3.2.1]octan-3-one (5 g, 35.92 mmol) in diethyl ether (12 mL) was added dropwise over 5 minutes. Cooling bath was removed and when internal temperature of −20° C. was reached the solution was quenched with 1N hydrochloric acid (200 mL). The aqueous layer was raised to pH=10 with ammonium hydroxide and extracted with diethyl ether (three times, 200 mL each). The combined organic layers were washed with brine (100 mL), dried with magnesium sulfate and concentrated to yield racemic3-(4-Chloro-phenyl)-8-methyl-8-aza-bicyclo[3.2.1]octan-3-ol (6.87 g, contains 9% 8-Methyl-8-aza-bicyclo[3.2.1]octan-3-one) as a white solid. Solid was used without further purification.

Aufarbeitung

  1. additionwas added dropwise over 20 minutes
  2. temperatureCooling bath
  3. customwas removed
  4. customwhen internal temperature of −20° C.
  5. customwas quenched with 1N hydrochloric acid (200 mL)
  6. temperatureThe aqueous layer was raised to pH=10 with ammonium hydroxide
  7. extractionextracted with diethyl ether (three times, 200 mL each)
  8. washThe combined organic layers were washed with brine (100 mL)
  9. dry with materialdried with magnesium sulfate
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-a5cf765acacb4ff29ab2a4397ecdaa8f
Quelldatensatz
uspto-grants-2003_04
Patentnummer
US06552015B2

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