Triisopropyl borate → 1-(Tetrahydropyran-2-yl)pyrazole-5-boronic acid

HRID 1530556Notes

Reaction equation

HRID 1530556 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:11]=[CH:10][CH:9]=[N:8]1.[Li]CCCC.[B:17](OC(C)C)([O:22]C(C)C)[O:18]C(C)C>C1COCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11]([B:17]([OH:22])[OH:18])=[CH:10][CH:9]=[N:8]1

Participants

5

Reactant 3

HCID 21531Triisopropyl borateHCID 218663101-(2-Tetrahydropyranyl)-1H-pyrazoleHCID 178418339Butyllithium

Product 1

HCID 467394631-(Tetrahydropyran-2-yl)pyrazole-5-boronic acidYield 133.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (2.10 g, 13.8 mmol) in anhydrous THF (30.0 mL) was added n-BuLi (2.5 M in hexane, 14.0 mL) at −78° C. The mixture was kept at this temperature for 30 min. Triisopropyl borate (2.85 g, 15.2 mmol) was added over 10 min at −78° C. and held for 1 hr. The resulting mixture was allowed to reach room temperature over 4 hr. After being quenched by aq. HCl (2.00 M, 55.0 mL) with intensive stirring, the aqueous phase was added NaCl (s) and extracted with THF/EtOAc. The combined organic layer was washed with brine, sat NaHCO3, dried over MgSO4, filtered and evaporated to afford 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-ylboronic acid (3.6 g, 52% yield) as yellow oil. LCMS (ESI) m/z: 197.0 [M+H+].

Workup

  1. waitheld for 1 hr
  2. waitto reach room temperature over 4 hr
  3. customAfter being quenched by aq. HCl (2.00 M, 55.0 mL) with intensive stirring
  4. additionthe aqueous phase was added NaCl (s)
  5. extractionextracted with THF/EtOAc
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-140022f10fe3492b80e6dbbf0296eeca
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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