1,1'-Carbonyldiimidazole → (R)-3-[2,2-Bis-(2-chloro-phenyl)-2-hydroxy-acetoxy]-1-(isoxazol-3-ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane bromide

HRID 660086Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])([OH:12])[C:9]([OH:11])=[O:10].C1N=CN(C(N2C=NC=C2)=O)C=1.[Br-:32].O[C@@H:34]1[CH:39]2[CH2:40][CH2:41][N+:36]([CH2:42][C:43](=[O:50])[NH:44][C:45]3[CH:49]=[CH:48][O:47][N:46]=3)([CH2:37][CH2:38]2)[CH2:35]1>CN(C=O)C>[Br-:32].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])([OH:12])[C:9]([O:11][C@@H:38]1[CH:39]2[CH2:40][CH2:41][N+:36]([CH2:42][C:43](=[O:50])[NH:44][C:45]3[CH:49]=[CH:48][O:47][N:46]=3)([CH2:35][CH2:34]2)[CH2:37]1)=[O:10]

Participants

Conditions

Temperature: 40 °C

Procedure

To a stirred solution of bis-(2-chloro-phenyl)-hydroxy-acetic acid (0.17 g, 0.572 mmol) in dry DMF (3 ml) under an inert atmosphere of Argon is added CDI (0.097 g, 0.6 mmol). After 1 hour, (R)-3-hydroxy-1-(isoxazol-3-ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane bromide (Intermediate A) (0.2 g, 0.602 mmol) is added and the reaction mixture is heated to 40° C. overnight. Purification using C-18 reverse phase column chromatography (eluent: water-acetonitrile) affords a solid which is triturated with diethyl ether to yield the titled compound as a crystalline solid.

Workup

customPurification
customaffords a solid which
customis triturated with diethyl ether

Sources & evidence

ORD record: ord-dc83dd847e454590b1430fe2fc08cffd
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08084463B2

Reaction notes

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