Hydrochloric Acid → 2-Fluoro-6-(4-nonylphenyl)pyridine-3-boronic acid

HRID 395246Notes

Reaction equation

HRID 395246 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:10][CH:9]=2)[N:3]=1.C([N-]C(C)C)(C)C.[Li+].[B:31](OC)([O:34]C)[O:32]C.Cl>C1COCC1.O>[F:1][C:2]1[C:7]([B:31]([OH:34])[OH:32])=[CH:6][CH:5]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:12][CH:13]=2)[N:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 2724682Lithium diisopropylamideHCID 181728412-Fluoro-6-(4-nonylphenyl)pyridine

Product 1

HCID 181728282-Fluoro-6-(4-nonylphenyl)pyridine-3-boronic acidYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 100 mol of 2-fluoro-6-(4-nonylphenyl)pyridine in 500 ml of dry THF is added dropwise to a solution of 110 mmol of lithium diisopropylamide in 100 ml of dry tetrahydrofuran at −70° C. under a protective gas atmosphere. The mixture is stirred for an additional 4 h at this temperature. A solution of 200 mmol of trimethyl borate in 40 ml of dry tetrahydrofuran is then added dropwise at a temperature of less than −60° C. The reaction mixture is then slowly warmed up to room temperature, admixed with a solution of 60 ml of water and 20 ml of concentrated hydrochloric acid while cooling with ice, and stirred for another hour at room temperature. The reaction mixture is extracted with tert-butyl methyl ether, the combined organic extracts are washed with water and saturated sodium chloride solution and dried with sodium sulfate, and the solvents are removed under reduced pressure. The raw product is crystallized from n-heptane/acetone 4:1, giving 19.8 g (58%) of 2-fluoro-6-(4-nonylphenyl)pyridine-3-boronic acid.

Workup

  1. temperaturewhile cooling with ice
  2. stirringstirred for another hour at room temperature
  3. extractionThe reaction mixture is extracted with tert-butyl methyl ether
  4. washthe combined organic extracts are washed with water and saturated sodium chloride solution
  5. dry with materialdried with sodium sulfate
  6. customthe solvents are removed under reduced pressure
  7. customThe raw product is crystallized from n-heptane/acetone 4:1

Sources & evidence

ORD record
ord-32d93b389cb74c7abb32fe8fbf2effa0
Source dataset
uspto-grants-2003_08
Patent number
US06605323B1

Reaction notes

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