Triethylamine → (3R)-3-[2-Benzyl-6-[(3S,4R)-3-chloro-4-methoxypyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinol

HRID 1359350Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1359350
[CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@@H:17]([Cl:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([C@:25]1([OH:33])[CH:30]2[CH2:31][CH2:32][N:27]([CH2:28][CH2:29]2)[CH2:26]1)#[CH:24].C(N(CC)CC)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C)C=O>[CH2:1]([C:8]1[C:13]([C:24]#[C:23][C@:25]2([OH:33])[CH:30]3[CH2:31][CH2:32][N:27]([CH2:28][CH2:29]3)[CH2:26]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@@H:17]([Cl:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 946095(3R)-3-ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 697586342-benzyl-6-[(3S,4R)-3-chloro-4-methoxypyrrolidine-1-yl]-3-iodopyridine

Produkt 1

HCID 69759480(3R)-3-[2-Benzyl-6-[(3S,4R)-3-chloro-4-methoxypyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinolAusbeute 36,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A mixture of 391 mg of 2-benzyl-6-[(3S,4R)-3-chloro-4-methoxypyrrolidine-1-yl]-3-iodopyridine, 152 mg of (3R)-3-ethynyl-3-quinuclidinol, 105 mg of tetrakis(triphenylphosphine)palladium(0), 9 mg of cuprous iodide, 0.38 ml of triethylamine and 5.0 ml of N,N-dimethylformamide was heated under stirring for 4 hours at 75° C. in a nitrogen atmosphere, followed by removing the solvent. The residue was subjected to NH-silica gel (Fuji Silicia) column chromatography and eluted with hexane/ethyl acetate (1:1) and then with ethyl acetate/methanol (20:1) and then crystallized from hexane/ethyl acetate, to give 150 mg of the target compound.

Aufarbeitung

  1. temperaturewas heated
  2. customby removing the solvent
  3. washeluted with hexane/ethyl acetate (1:1)
  4. customwith ethyl acetate/methanol (20:1) and then crystallized from hexane/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-45d80c7c24334d2490241a6d23b48a36
Quelldatensatz
uspto-grants-2003_07
Patentnummer
US06599917B1

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