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

HRID 722193Notes

Reaction equation

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]

Participants

Conditions

Temperature: 85 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-f2b2e38ec9ee40f9b1f25029cf5227c9
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07138410B2

Reaction notes

Loading…