Tetrafluoroboric acid → MUT-37307

HRID 1023994Notes

Reaction equation

HRID 1023994 reaction equation
N[C:2]1[C:7]([O:8][C:9]2[CH:14]=[C:13]([F:15])[C:12]([CH2:16][CH3:17])=[CH:11][C:10]=2[OH:18])=[CH:6][CH:5]=[CH:4][N:3]=1.[F:19][B-](F)(F)F.[H+].N([O-])=O.[Na+]>C(O)(=O)C>[CH2:16]([C:12]1[C:13]([F:15])=[CH:14][C:9]([O:8][C:7]2[C:2]([F:19])=[N:3][CH:4]=[CH:5][CH:6]=2)=[C:10]([OH:18])[CH:11]=1)[CH3:17]

Participants

5

Reactant 3

HCID 28118Tetrafluoroboric acidHCID 23668193Sodium NitriteHCID 59191218HCID 59191218, compound

Product 1

HCID 25020641MUT-37307Yield 17.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-(2-aminopyridin-3yloxy)-5-ethyl-4-fluorophenol (45 mg, 0.18 mmol) in glacial acetic acid (2.5 ml) was added 0.36 ml of tetrafluoroboric acid (48% in water). The reaction mixture was cooled to 0° C. and sodium nitrite (18 mg, 0.27 mmol) was added at 0° C. and stirred at 0° C. for 1.5 hours until reaction was complete on TLC. The reaction mixture was quenched by adding ice and sodium bicarbonate solution and stirred for 10 minutes before extracting the aqueous solution with ethylacetate. The combined ethyl acetate fraction was washed with saturated sodium bicarbonate solution, water, followed by brine, dried over anhydrous sodium sulfate and concentrated in vacuo to get the crude compound. The crude material was column purified over silica gel using Petroleum ether/ethyl acetate 9:1 as eluant and then further purified by preparative HPLC using 0.1% TFA in water and acetonitrile as solvent system to get 8 mg (17.6%) of 5-Ethyl-4-fluoro-2-(2-fluoropyridin-3yloxy)phenol as a white solid.

Workup

  1. customThe reaction mixture was quenched
  2. additionby adding ice and sodium bicarbonate solution
  3. stirringstirred for 10 minutes
  4. extractionbefore extracting the aqueous solution with ethylacetate
  5. washThe combined ethyl acetate fraction was washed with saturated sodium bicarbonate solution, water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto get the crude compound
  9. custompurified over silica gel
  10. customfurther purified by preparative HPLC

Sources & evidence

ORD record
ord-40d9c128be624446b4165430226ddcf7
Source dataset
uspto-grants-2014_05
Patent number
US08722746B2

Reaction notes

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