Diisopropylamine → 2-Fluoro-5-methoxypyridine-3-boronic acid

HRID 1621943

Reaction equation

HRID 1621943 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][N:15]=1.[B:22](OC(C)C)([O:27]C(C)C)[O:23]C(C)C>C1COCC1>[F:13][C:14]1[C:19]([B:22]([OH:27])[OH:23])=[CH:18][C:17]([O:20][CH3:21])=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 21531Triisopropyl borateHCID 189731092-Fluoro-5-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 574973352-Fluoro-5-methoxypyridine-3-boronic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 100 mL round-bottomed flask, diisopropylamine (Aldrich, 1.40 mL, 9.99 mmol) was dissolved into THF (6 mL). nBuLi (Aldrich, 2.5 M in hexanes, 3.60 mL, 8.99 mmol) was added slowly at 0° C. The mixture was stirred at 0° C. for 30 min then cooled to −78° C. 2-fluoro-5-methoxypyridine (0.520 g, 4.09 mmol) in 4 mL of THF was added slowly, and the mixture was stirred at that temperature for 40 min. Triisopropyl borate (Aldrich, 2.07 mL, 8.99 mmol) in a total of 4 mL of THF was added slowly and the mixture was stirred at −78° C. for 5 min. The cold bath was removed and the reaction mixture was stirred at room temperature for 1 h. 1 N NaOH (20 mL) was added to the mixture to quench the reaction. The layers were separated and the aqueous phase was treated with 5N HCl to adjust the pH to around 5. The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to afford 0.593 g of tan color solid. This material was used in the next step without further purification.

Workup

  1. temperaturethen cooled to −78° C
  2. stirringthe mixture was stirred at that temperature for 40 min
  3. stirringthe mixture was stirred at −78° C. for 5 min
  4. customThe cold bath was removed
  5. stirringthe reaction mixture was stirred at room temperature for 1 h
  6. addition1 N NaOH (20 mL) was added to the mixture
  7. customto quench
  8. customthe reaction
  9. customThe layers were separated
  10. additionthe aqueous phase was treated with 5N HCl
  11. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  12. dry with materialThe combined organic phases were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto afford 0.593 g of tan color solid
  16. customThis material was used in the next step without further purification

Sources & evidence

ORD record
ord-7bd1722ddee34de896fb4a9ea106adee
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Linked notes

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