Potassium Carbonate → 3,5-Difluoro-4-[2-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)ethoxy]benzonitrile hydrochloric acid salt

HRID 2078407Notes

Reaction equation

Br[CH2:2][CH2:3][O:4][C:5]1[C:12]([F:13])=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[F:14].[ClH:15].C(OC([N:23]1[CH2:30][CH:29]2[O:31][CH:25]([CH2:26][NH:27][CH2:28]2)[CH2:24]1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[ClH:15].[F:14][C:6]1[CH:7]=[C:8]([CH:11]=[C:12]([F:13])[C:5]=1[O:4][CH2:3][CH2:2][N:27]1[CH2:26][CH:25]2[O:31][CH:29]([CH2:30][NH:23][CH2:24]2)[CH2:28]1)[C:9]#[N:10]

Participants

Conditions

Temperature: 60 °C

Procedure

A suspension of 4-(2-bromoethoxy)-3,5-difluorobenzonitrile (12 g, 45.8 mmol; see step (i) above), 9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester HCl-salt (11.5 g, 0.0435 mol; see WO 01/28992) and dry K2CO3 (25.32 g, 0.183 mol) in 140 mL of dry acetonitrile was stirred at 60° C. for five days under a nitrogen atmosphere. The reaction mixture was filtered through Celite® and the filtrate was then concentrated under reduced pressure. The residue was purified by column chromatography over silica gel, using 20% ethyl acetate in petroleum ether as eluent, to yield 12.55 g of the sub-title compound as a white solid.

Workup

filtrationThe reaction mixture was filtered through Celite®
concentrationthe filtrate was then concentrated under reduced pressure
customThe residue was purified by column chromatography over silica gel

Sources & evidence

ORD record: ord-279b4c14abe9479ea0a2eee454426c93
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07928225B2

Reaction notes

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