Azetidine → (R)-(-)-5'-(1-Azetidinyl)spiro[1-azabicyclo[2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine]

HRID 49612

Reaktionsgleichung

Reaktionsgleichung von HRID 49612
Br[C:2]1[CH:3]=[C:4]2[CH2:10][C@:9]3([CH:15]4[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]4)[CH2:11]3)[O:8][C:5]2=[N:6][CH:7]=1.[NH:18]1[CH2:21][CH2:20][CH2:19]1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCCC1>[N:18]1([C:2]2[CH:3]=[C:4]3[CH2:10][C@:9]4([CH:15]5[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]5)[CH2:11]4)[O:8][C:5]3=[N:6][CH:7]=2)[CH2:21][CH2:20][CH2:19]1

Komponenten

7

Edukt 4

HCID 10422AzetidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 54506690(2R)-5'-bromo-3'H-spiro[4-azabicyclo[2.2.2]octane-2,2'-furo[2,3-b]pyridine]

Produkt 1

HCID 53881099(R)-(-)-5'-(1-Azetidinyl)spiro[1-azabicyclo[2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine]

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

(R)-(−)-5′-Bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (295 mg, 1 mmol), azetidine (0.101 mL, 1.5 mmol), sodium tert-butoxide (135 mg, 1.4 mmol), tris(dibenzylideneacetone)dipalladium (46 mg, 0.05 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (62 mg, 0.1 mmol) and anhydrous tetrahydrofuran (9 mL) were combined in a heavy-walled threaded glass tube containing a magnetic stir bar, purged with argon, and sealed with a Teflon plug and FETFE O-ring. The mixture was stirred and heated at 75° C. for 4 hours, cooled to room temperature, dissolved in chloroform (20 mL), washed with brine (3×10 mL), dried (MgSO4), evaporated under reduced pressure, and purified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol 95:5) to procure the title compound (230 mg, 0.0.85 mmol, 85%) as a light tan solid: chemical ionization MS (m/z, relative intensity) 272 ([MH]+, 56).

Aufarbeitung

  1. additioncontaining a magnetic stir bar
  2. custompurged with argon
  3. customsealed with a Teflon plug and FETFE O-ring
  4. temperaturecooled to room temperature
  5. dissolutiondissolved in chloroform (20 mL)
  6. washwashed with brine (3×10 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated under reduced pressure
  9. custompurified by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol 95:5)

Quellen und Nachweise

ORD-Eintrag
ord-b46c85aa9059404586ea4e38886d37b2
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06706878B2

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