Benzyl Bromide → (1R*,2R*,5R*)-8-Benzyl-2-[2,5-bis(trifluoromethyl)phenylmethoxy]-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088134

Reaktionsgleichung

Reaktionsgleichung von HRID 2088134
[CH2:1]([N:8]1[C@@H:13]2[CH2:14][CH2:15][C@@:9]1([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C@H:10]([OH:16])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[F:25][C:26]([F:40])([F:39])[C:27]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][C:28]=1[CH2:29]Br.C(Br)C1C=CC=CC=1>O.C1COCC1>[CH2:1]([N:8]1[C@@H:13]2[CH2:14][CH2:15][C@@:9]1([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C@H:10]([O:16][CH2:29][C:28]1[CH:31]=[C:32]([C:35]([F:37])([F:38])[F:36])[CH:33]=[CH:34][C:27]=1[C:26]([F:25])([F:39])[F:40])[CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 27731992-(Bromomethyl)-1,4-bis(trifluoromethyl)benzeneHCID 69688994(1R*,2R*,5R*)-8-Benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol

Produkt 1

HCID 86586657(1R*,2R*,5R*)-8-Benzyl-2-[2,5-bis(trifluoromethyl)phenylmethoxy]-1-phenyl-8-azabicyclo[3.2.1]octane

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

(1R*,2R*,5R*)-8-Benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 9; 151 mg, 0.52 mmol) was treated with sodium hydride (41 mg, 60% in oil, 1.03 mmol) at 0° C. in a solution of THF (2 ml) and allowed to warm to room temperature. The mixture was recooled to 0° C. and 2,5-bis(trifluoromethyl)benzyl bromide (0.24 ml, 1.30 mmol) added and the mixture heated to 50° C. for 2 days. A further 1.30 mmol of the benzyl bromide was added and the mixture further heated for 50° C. for 2 days. The reaction mixture was poured into water and extracted with ethyl acetate (×3), dried (MgSO4) and concentrated in vacuo to give a yellow solid. This was purified by flash column chromatography [25% ethyl acetate in iso-hexane] to give the title compound.

Aufarbeitung

  1. customwas recooled to 0° C.
  2. temperaturethe mixture heated to 50° C. for 2 days
  3. temperaturethe mixture further heated for 50° C. for 2 days
  4. extractionextracted with ethyl acetate (×3)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give a yellow solid
  8. customThis was purified by flash column chromatography [25% ethyl acetate in iso-hexane]

Quellen und Nachweise

ORD-Eintrag
ord-3985ac8dd7a14528a1ab2784fd7fa7cb
Quelldatensatz
uspto-grants-2004_04
Patentnummer
US06727249B2

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