Cesium carbonate → 3-[[3,5-Difluoro-6-(3-(1-methylimidazolin-2-yl)phenoxy)4-[(2,2-dimethyldioxolan-4-yl)methoxy]pyridin-2-yl]oxy]4-(benzyloxy)benzonitrile

HRID 1267091Notes

Reaction equation

HRID 1267091 reaction equation
[F:1][C:2]1[C:3]([O:19][C:20]2[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=2[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:23]#[N:24])=[N:4][C:5](F)=[C:6]([F:17])[C:7]=1[O:8][CH2:9][CH:10]1[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11]1.C([O-])([O-])=O.[Cs+].[Cs+].[OH:42][C:43]1[CH:44]=[C:45]([C:49]2[N:50]([CH3:54])[CH2:51][CH2:52][N:53]=2)[CH:46]=[CH:47][CH:48]=1>CS(C)=O>[F:1][C:2]1[C:3]([O:19][C:20]2[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=2[O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:23]#[N:24])=[N:4][C:5]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([C:49]3[N:50]([CH3:54])[CH2:51][CH2:52][N:53]=3)[CH:44]=2)=[C:6]([F:17])[C:7]=1[O:8][CH2:9][CH:10]1[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 114238803-(1-Methylimidazolin-2-yl)phenolHCID 695506003-[[3,5,6-Trifluoro-4-[(2,2-dimethyldioxolan-4-yl)methoxy]pyridin-2-yl]oxy]-4-(benzyloxy)benzonitrile

Product 1

HCID 120165153-[[3,5-Difluoro-6-(3-(1-methylimidazolin-2-yl)phenoxy)4-[(2,2-dimethyldioxolan-4-yl)methoxy]pyridin-2-yl]oxy]4-(benzyloxy)benzonitrileYield 66.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
55 °C

Procedure

To 3-[[3,5,6-trifluoro-4-[(2,2-dimethyidioxolan-4-yl)methoxy]pyridin-2-yl]oxy]4-(benzyloxy)benzonitrile (1.0 g, 2.1 mmol) in DMSO (6 mL) was added Cs2CO3 (0.7 g, 2.1 mmol) and 2-(3-hydroxyphenyl)-1-methylimidazoline (0.4 g, 2.2 mmol). After stirring in an oil bath at 55° C. for 24 hours, the reaction was partitioned with water and ethyl acetate. The layers were separated, washed with water and brine, dried (Na2SO4), and the solvent was removed in vacuo. The residue was chromatographed on silica with CH2Cl2/MeOH/NH4OH (240/10/1) to give 3-[[3,5-difluoro-6-(3-(1-methylimidazolin-2-yl)phenoxy)-4-(2,2-dimethyidioxolan-4-yl)methoxylpyridin-2-yl]oxy]4-(benzyloxy)benzonitrile (0.9 g).

Workup

  1. customthe reaction was partitioned with water and ethyl acetate
  2. customThe layers were separated
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. customthe solvent was removed in vacuo
  6. customThe residue was chromatographed on silica with CH2Cl2/MeOH/NH4OH (240/10/1)

Sources & evidence

ORD record
ord-c6d8fb33e6dd4d0098dfe232802b623f
Source dataset
uspto-grants-2003_04
Patent number
US06552030B2

Reaction notes

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