18-Crown-6 → Tert-butyl 3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 1748154Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1748154
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH:12]2[CH2:13][CH:14]([OH:16])[CH2:15][CH:9]1[CH2:10][CH2:11]2)=[O:7])([CH3:4])[CH3:3].C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].Br[CH2:42][C:43]1[C:44]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[O:57][C:58]([F:61])([F:60])[F:59])=[N:45][O:46][C:47]=1[CH:48]1[CH2:50][CH2:49]1>O1CCCC1>[CH:48]1([C:47]2[O:46][N:45]=[C:44]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=3[O:57][C:58]([F:61])([F:60])[F:59])[C:43]=2[CH2:42][O:16][CH:14]2[CH2:15][CH:9]3[N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH:12]([CH2:11][CH2:10]3)[CH2:13]2)[CH2:49][CH2:50]1

Komponenten

6

Edukt 4

HCID 2855718-Crown-6HCID 21187725tert-Butyl 3-hydroxy-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 23665647Potassium tert-butoxideHCID 669060924-(Bromomethyl)-5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]isoxazole

Produkt 1

HCID 67983217Tert-butyl 3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A 250-mL flask was purged with nitrogen and then charged with N-Boc-nortropine (2.9 g, 12.8 mmol), 18-Crown-6 (3.4 g, 12.8 mmol), and anhydrous tetrahydrofuran (80 mL). Potassium tert-butoxide (2.9 g, 25.6 mmol) was added in small portions, and the mixture was stirred vigorously under nitrogen fo(1 h. 4-(bromomethyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)-phenyl)isoxazole (4.18 g, 11.6 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) and added dropwise, and the reaction mixture was stirred overnight under a positive nitrogen pressure. The solvent was removed in vacuo and the mixture diluted with water (100 mL) and ethyl acetate (100 mL). The organic layer was separated, dried with anhydrous MgSO4, and evaporated in vacuo. The crude residue was purified by silica gel chromatography using a gradient of 0-100% ethyl acetate/hexanes to yield the desired product as yellow oil. MS m/z 509.2 (M+1).

Aufarbeitung

  1. customA 250-mL flask was purged with nitrogen
  2. custom1 h
  3. additionadded dropwise
  4. stirringthe reaction mixture was stirred overnight under a positive nitrogen pressure
  5. customThe solvent was removed in vacuo
  6. additionthe mixture diluted with water (100 mL) and ethyl acetate (100 mL)
  7. customThe organic layer was separated
  8. dry with materialdried with anhydrous MgSO4
  9. customevaporated in vacuo
  10. customThe crude residue was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-dc15b7ebd1cf4ad388f859f113845528
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150568B2

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