Potassium Carbonate → 7-[2-(4-Cyano-2-fluoro-phenoxy)-ethyl]-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester

HRID 1992366Notes

Reaction equation

Br[CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[F:13].[C:14]([O:18][C:19]([N:21]1[CH2:28][CH:27]2[O:29][CH:23]([CH2:24][NH:25][CH2:26]2)[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+]>C(#N)C>[C:14]([O:18][C:19]([N:21]1[CH2:22][CH:23]2[O:29][CH:27]([CH2:26][N:25]([CH2:2][CH2:3][O:4][C:5]3[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=3[F:13])[CH2:24]2)[CH2:28]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

Conditions

Temperature: 60 °C

Procedure

A suspension of 4-(2-Bromo-ethoxy)-3-fluoro-benzonitrile (21.6 g, 0.0885 mol, from step (v) above), 9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (21.1 g, 0.07965 mol; see WO 01/28992) and dry K2CO3 (48.9 g, 0.354 mol) in 200 ml of dry acetonitrile was stirred at 60° C. for five days under N2 atmosphere. The reaction mixture was filtered through celite and filtrate was concentrated under reduced pressure. The residue was purified by column chromatography over silica gel using 27% ethyl acetate in petroleum ether, as eluent to yield the sub-title compound (20.5 g) as a solid.

Workup

filtrationThe reaction mixture was filtered through celite and filtrate
concentrationwas concentrated under reduced pressure
customThe residue was purified by column chromatography over silica gel using 27% ethyl acetate in petroleum ether, as eluent

Sources & evidence

ORD record: ord-e4becfefd4f944aeb1fc3ee09fcd2a88
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07648985B2

Reaction notes

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