Hexane → 1-cycloheptyl-3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]oct-3-yl]-1-phenyl-2-propyn-1-ol

HRID 900774

Reaktionsgleichung

Reaktionsgleichung von HRID 900774
[Li]CCCC.CCCCCC.[CH3:12][O:13][C@@:14]1([C:22]#[CH:23])[CH:19]2[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]2)[CH2:15]1.[CH:24]1([C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:32])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>C1COCC1>[CH:24]1([C:31]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)([OH:32])[C:23]#[C:22][C@:14]2([O:13][CH3:12])[CH:19]3[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]3)[CH2:15]2)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]1

Komponenten

6

Edukt 4

HCID 8058HexaneHCID 297753Cycloheptyl(phenyl)methanoneHCID 9812856(3R)-3-ethynyl-1-azabicyclo[2.2.2]oct-3-yl methyl etherHCID 178418339Butyllithium

Produkt 1

HCID 692923921-cycloheptyl-3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]oct-3-yl]-1-phenyl-2-propyn-1-ol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-5 °C

Versuchsvorschrift

A 1.6 N solution of BuLi in hexane (41.7 ml, 66.7 mmol) was added dropwise to a solution of (3R)-3-ethynyl-1-azabicyclo[2.2.2]oct-3-yl methyl ether 53 (11 g, 66.7 mmol) in THF (100 ml) cooled at −5° C. After stirring for 10 minutes, the medium was cooled at −15° C., and a solution of cycloheptyl(phenyl)methanone 44 (14.2 g, 70.2 mmol) in THF (50 ml) was slowly added. The cooling bath was removed and the reaction was allowed to gradually warm to room temperature during 2 hours. The reaction was quenched by the addition of saturated aqueous NH4Cl solution. The reaction mixture was washed with brine, dried over Na2SO4 and evaporated. The yellowish oil was purified by chromatography over silica gel (CH2Cl2/EtOH/NH4OH 94/6/1). 1-cycloheptyl-3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]oct-3-yl]-1-phenyl-2-propyn-1-ol 116 was obtained as a white solid (20.35 g, 83%, mixture of diastereomers).

Aufarbeitung

  1. temperaturethe medium was cooled at −15° C.
  2. customThe cooling bath was removed
  3. temperatureto gradually warm to room temperature during 2 hours
  4. customThe reaction was quenched by the addition of saturated aqueous NH4Cl solution
  5. washThe reaction mixture was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe yellowish oil was purified by chromatography over silica gel (CH2Cl2/EtOH/NH4OH 94/6/1)

Quellen und Nachweise

ORD-Eintrag
ord-0b5f7c8ca8064a15b6e47d696e40695f
Quelldatensatz
uspto-grants-2008_04
Patentnummer
US07361668B2

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