Ammonia → (3r)-3-[2-Benzyl-6-[(3r,4r)-3,4-difluoropyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinol

HRID 1359344Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1359344
[CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([F:20])[C@H:17]([F:21])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([C@:24]1([OH:32])[CH:29]2[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]2)[CH2:25]1)#[CH:23].C(N(CC)CC)C.N>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.CO>[CH2:1]([C:8]1[C:13]([C:23]#[C:22][C@:24]2([OH:32])[CH:29]3[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]3)[CH2:25]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([F:20])[C@H:17]([F:21])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 946095(3R)-3-ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 697590462-benzyl-6-[(3R,4R)-3,4-difluoropyrrolidine-1-yl]-3-iodopyridine

Produkt 1

HCID 59077824(3r)-3-[2-Benzyl-6-[(3r,4r)-3,4-difluoropyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinolAusbeute 40,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A mixture of 152 mg of 2-benzyl-6-[(3R,4R)-3,4-difluoropyrrolidine-1-yl]-3-iodopyridine, 60 mg of (3R)-3-ethynyl-3-quinuclidinol, 22 mg of tetrakis(triphenylphosphine)palladium(0), 7 mg of cuprous iodide, 106 μl of triethylamine and 1.5 ml of methanol was heated under stirring for 3 hours at 75° C. in a nitrogen atmosphere. The reaction solution was poured into an aqueous dilute ammonia and then extracted with ethyl acetate. The extract was washed with brine and the solvent was removed. The residue was subjected to NH-silica gel (Fuji Silicia) column chromatography, eluted with hexane/ethyl acetate (1:1) and then with ethyl acetate/methanol (15:1) and crystallized from hexane/ethyl acetate, to give 65 mg of the target compound.

Aufarbeitung

  1. temperaturewas heated
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with brine
  4. customthe solvent was removed
  5. washeluted with hexane/ethyl acetate (1:1)
  6. customwith ethyl acetate/methanol (15:1) and crystallized from hexane/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-eb90d345477c41f7823cd30dd8ae279d
Quelldatensatz
uspto-grants-2003_07
Patentnummer
US06599917B1

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