Hydrochloric Acid → 2-Fluoropyridine-3-boronic acid

HRID 52132

Reaction equation

HRID 52132 reaction equation
[Li]CCCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[B:13](OC)([O:16]C)[O:14]C.Cl>C1COCC1.O.C1COCC1>[F:6][C:7]1[C:12]([B:13]([OH:16])[OH:14])=[CH:11][CH:10]=[CH:9][N:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 97462-FluoropyridineHCID 178418339Butyllithium

Product 1

HCID 27832702-Fluoropyridine-3-boronic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
-78 °C

Procedure

800 ml (1.28 mol) of n-BuLi (1.6M in hexane) are added to a solution of 188 ml (1.32 mol) of TMP in 1,000 ml of THF at -78° C. under argon. After the mixture has been stirred for 45 minutes at this temperature, 120.4 g (1.24 mol) of 2-fluoropyridine in 200 ml of THF are added in the course of 3 minutes. After the mixture has been stirred for 4 hours at -78° C., a solution of 128.8 g (1.24 mol) of trimethyl borate in 200 ml of THF is added dropwise in the course of 20 minutes. Then, 200 ml of a 1: 1 mixture of water/THF is added at 25° C., and 256 ml of concentrated HCl are added dropwise, with ice-cooling. The organic phase is separated off, and the aqueous phase is washed twice using Et2O, filtered and concentrated in vacuo. Crude yield 148.2 g.

Workup

  1. additionare added in the course of 3 minutes
  2. additionis added at 25° C.
  3. temperaturecooling
  4. customThe organic phase is separated off
  5. washthe aqueous phase is washed twice using Et2O
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-795d1700bda843fc9c46358a5d1176d3
Source dataset
uspto-grants-1997_04
Patent number
US05616590

Linked notes

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