Sodium Hydroxide → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-[3-(methoxy)phenyl]-1-benzofuran-2-carboxamide hydrochloride

HRID 2179655Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].[ClH:14].[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[C@@H:17]([NH:23][C:24]([C:26]1[O:27][C:28]3[CH:34]=[CH:33][C:32](Br)=[CH:31][C:29]=3[CH:30]=1)=[O:25])[CH2:16]2>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]>[ClH:14].[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[C@@H:17]([NH:23][C:24]([C:26]1[O:27][C:28]3[CH:34]=[CH:33][C:32]([C:7]4[CH:6]=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:8]=4)=[CH:31][C:29]=3[CH:30]=1)=[O:25])[CH2:16]2

Participants

Conditions

Temperature: 90 °C

Procedure

130 mg (0.86 mmol) of 3-(methoxy)phenylboronic acid and 2.15 ml of 1N sodium hydroxide solution are added to a mixture of 250 mg (0.72 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-bromo-1-benzofuran-2-carboxamide (Example 3A) and 52 mg (0.07 mmol) of PdCl2(dppf) in 3 ml of DMF. The reaction mixture is heated at 90° C. overnight. The solvent is removed under reduced pressure, and the crude product is taken up in methanol and filtered through kieselguhr. Purification takes place by preparative HPLC. The product fractions are mixed with an excess of 1N hydrochloric acid. The solvent is removed under reduced pressure. Drying under high vacuum results in 208 mg (63% of theory) of the title compound.

Workup

customThe solvent is removed under reduced pressure
filtrationfiltered through kieselguhr
customPurification
additionThe product fractions are mixed with an excess of 1N hydrochloric acid
customThe solvent is removed under reduced pressure
customDrying under high vacuum

Sources & evidence

ORD record: ord-8ef979263198467284d8c8952f145e8f
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067931B2

Reaction notes

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