Potassium Carbonate → Tetraisopropyl (2-(5-(3,5-dimethylisoxazol-4-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)

HRID 2410257Notes

Reaction equation

HRID 2410257 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][C:9]([P:21](=[O:30])([O:26][CH:27]([CH3:29])[CH3:28])[O:22][CH:23]([CH3:25])[CH3:24])([P:11](=[O:20])([O:16][CH:17]([CH3:19])[CH3:18])[O:12][CH:13]([CH3:15])[CH3:14])[F:10])[CH:5]=[N:6][CH:7]=1.[CH3:31][C:32]1[C:36](B(O)O)=[C:35]([CH3:40])[O:34][N:33]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC>[CH3:31][C:32]1[C:36]([C:2]2[CH:3]=[C:4]([CH2:8][C:9]([P:21](=[O:30])([O:22][CH:23]([CH3:24])[CH3:25])[O:26][CH:27]([CH3:29])[CH3:28])([P:11](=[O:20])([O:16][CH:17]([CH3:18])[CH3:19])[O:12][CH:13]([CH3:15])[CH3:14])[F:10])[CH:5]=[N:6][CH:7]=2)=[C:35]([CH3:40])[O:34][N:33]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 86691496Tetraisopropyl(2-(5-bromopyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)

Product 1

HCID 86691497Tetraisopropyl (2-(5-(3,5-dimethylisoxazol-4-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)Yield 47%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A sample of tetraisopropyl (2-(5-bromopyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate) (85 mg; 0.16 mmol), Pd(Ph3)4 (36.9 mg; 0.032 mmol) and (3,5-dimethylisoxazol-4-yl)boronic acid (34 mg; 0.24 mmol) are added in a vial, the vial is capped with a septum and added DME (4 mL) is added. The mixture is immediately flushed with argon, potassium carbonate solution (2.5 eq.) is added and flushed again with argon. The reaction mixture is stirred at 80° C. for 36 h under argon. The mixture is cooled, diluted with EtOAc and filtered through Celite™, the Celite™ is rinsed 3× with EtOAc/MeOH (1:1). The combined filtrate is concentrated under vacuum and deposited on silica gel. Purification by column chromatography on silica gel (pre washed with 1% NEt3 in hexanes) using a solvent gradient from hexanes to EtOAc, and then to 50% MeOH in EtOAc lead to the isolation of the product as a brown oil (41 mg; 47% yield).

Workup

  1. customis capped with a septum
  2. additionis added
  3. additionis added
  4. customflushed again with argon
  5. temperatureThe mixture is cooled
  6. additiondiluted with EtOAc
  7. filtrationfiltered through Celite™
  8. washthe Celite™ is rinsed 3× with EtOAc/MeOH (1:1)
  9. concentrationThe combined filtrate is concentrated under vacuum
  10. customPurification by column chromatography on silica gel (pre washed with 1% NEt3 in hexanes)

Sources & evidence

ORD record
ord-31cf19ce63bd4e5e9d8c6a232515eb9b
Source dataset
uspto-grants-2014_08
Patent number
US08816082B2

Reaction notes

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