Lithium Hydroxide → [2-(2-tert-Butylphenoxy)pyridin-3-yl]boronic acid

HRID 555427Notes

Reaction equation

HRID 555427 reaction equation
[C:1]([C:5]1[CH:18]=[CH:17][CH:16]=[CH:15][C:6]=1[O:7][C:8]1[C:13](I)=[CH:12][CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.CCCCC.[B:29](OC(C)C)([O:34]C(C)C)[O:30]C(C)C.[Li+].[OH-]>C1COCC1.O>[C:1]([C:5]1[CH:18]=[CH:17][CH:16]=[CH:15][C:6]=1[O:7][C:8]1[C:13]([B:29]([OH:34])[OH:30])=[CH:12][CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 8003PentaneHCID 21531Triisopropyl borateHCID 598574352-(2-tert-Butylphenoxy)-3-iodopyridineHCID 178418339Butyllithium

Product 1

HCID 57416450[2-(2-tert-Butylphenoxy)pyridin-3-yl]boronic acidYield 92.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 141a (3.35 g, 9.49 mmol) in THF (60 ml) under nitrogen at −78° C. was added 2.0 M nBuLi in pentane (14.2 mL, 28.47 mmol, 3 eq) over ˜3 min. The reaction was stirred at −78° C. for 10 min & then B(OiPr)3 (6.54 mL, 28.47 mmol, 3 eq) was added in a single aliquot. The reaction was stirred at −78° C. for 40 min and then the reaction was poured into water (˜60 mL) followed by the addition of LiOH (˜3.5 g). The reaction was stirred for 2 h at rt. Partition the reaction mixture between water (˜200 mL additional) and EtOAc (˜200 mL). Separate layers and wash the aqueous once more with EtOAc. Pour aqueous into a large erlenmyer flask & add EtOAc (˜200 mL). With vigorous stirring add conc. HCl dropwise until pH ˜2. Separate layers in sep. funnel & extract aqueous once more with EtOAc (˜200 mL). Combine these last two EtOAc extracts, dry over sodium sulfate, filter and concentrate. Azeotrope twice with toluene to give 234b (2.38 g) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.31 (s, 9H); 4.1 (bs, 1H); 5.61 (bs, 1H); 6.91 (d, J=7.47 Hz, 1H); 7.05 (dd, J=6.37, 3.74 Hz, 1H); 7.15-7.3 (m, 2H); 7.48 (dd J=7.47, 1.32 Hz, 1H); 8.23 (bs, 1H); 8.27 (dd, J=7.03 Hz, 1H).

Workup

  1. stirringThe reaction was stirred at −78° C. for 40 min
  2. stirringThe reaction was stirred for 2 h at rt
  3. customPartition the reaction mixture between water (˜200 mL additional) and EtOAc (˜200 mL)
  4. washSeparate layers and wash the aqueous once more with EtOAc
  5. additionPour aqueous into a large erlenmyer flask & add EtOAc (˜200 mL)
  6. stirringWith vigorous stirring
  7. additionadd conc. HCl dropwise until pH ˜2
  8. extractionfunnel & extract aqueous once more with EtOAc (˜200 mL)
  9. dry with materialCombine these last two EtOAc extracts, dry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate

Sources & evidence

ORD record
ord-4207ef25bd3a4701877886fcddbe2fda
Source dataset
uspto-grants-2011_11
Patent number
US08053450B2

Reaction notes

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