Potassium Carbonate → (3R)-N-[4'-(Hydroxymethyl)-3'-fluoro-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide

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Reaktionsgleichung

B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][OH:33])=[C:28]([F:34])[CH:27]=1.Br[C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]([C@@H:45]2[CH:50]3[CH2:51][CH2:52][N:47]([CH2:48][CH2:49]3)[CH2:46]2)=[O:44])=[CH:38][CH:37]=1.[OH-].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:33][CH2:32][C:29]1[CH:30]=[CH:31][C:26]([C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:43]([C@@H:45]3[CH:50]4[CH2:51][CH2:52][N:47]([CH2:48][CH2:49]4)[CH2:46]3)=[O:44])=[CH:38][CH:37]=2)=[CH:27][C:28]=1[F:34]

Komponenten

Reaktionsbedingungen

Temperatur: 85 °C

Versuchsvorschrift

492 mg (1.62) of bis(pinacolato)diboron, 804 mg (5.82 mmol) of dry potassium carbonate, and 398 mg (1.94 mmol) of (4-bromo-2-fluorophenyl)methanol are dissolved in 4.2 ml of DMF. Argon is passed through the reaction mixture for 15 minutes, and then 59 mg (0.08 mmol) of PdCl2(dppf) are added, and the mixture is heated at 85° C. overnight. Then, 500 mg (1.62 mmol) of (3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide, 8.1 ml of 1N sodium hydroxide solution and a further 59 mg (0.02 mmol) of PdCl2(dppf) are added. The mixture is heated at 85° C. overnight. The solvent is removed under reduced pressure. The crude product is purified by preparative HPLC. 21 mg (3% of theory) of the title compound are obtained.

Aufarbeitung

temperatureThe mixture is heated at 85° C. overnight
customThe solvent is removed under reduced pressure
customThe crude product is purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag: ord-f2b2e38ec9ee40f9b1f25029cf5227c9
Quelldatensatz: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US07138410B2

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