Hydrochloric Acid → 4-(Trifluoromethoxy)phenylboronic acid

HRID 2306078Notes

Reaction equation

HRID 2306078 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[B:13](OC(C)C)([O:18]C(C)C)[O:14]C(C)C.C([Li])CCC.Cl.[Cl-].[Na+]>C1COCC1.CCCCCCC>[F:10][C:9]([F:12])([F:11])[O:8][C:5]1[CH:6]=[CH:7][C:2]([B:13]([OH:18])[OH:14])=[CH:3][CH:4]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 21531Triisopropyl borateHCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 178418339Butyllithium

Product 1

HCID 27343864-(Trifluoromethoxy)phenylboronic acidYield 90.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Procedure

A solution of 1-bromo-4-(trifluoromethoxy)benzene (1.69 kg) and triisopropyl borate (1.46 kg) in THF (6.75 L) at −70° C. was treated with 2.25 M butyllithium in hexanes (3.27 L) over 2.3 hours, stirred for 10 minutes, treated with 6M HCl (1.52 L) over 50 minutes, stirred for 18 hours at room temperature, and poured into a mixture of heptane (8.43 L) and 20% (w/w) sodium chloride (8.44 kg). This mixture was stirred for 10 minutes and separated into an aqueous fraction and an organic fraction. The organic fraction was concentrated to provide a white paste. The paste was dried under vacuum (100 mmHg) at ambient temperature with a nitrogen bleed for 2 days then at 40-50° C. for 18 hours to provide 1.306 kg (90.4%) of the desired product as a solid. 1H NMR (CDCl3, 300 MHz) δ7.24-7.19 (m, 2H), 8.14-8.10 (m, 2H) with additional absorptions at 7.19-7.15 (m, 2H) and 8.04-8.00 (m, 2H) corresponding to the cyclic boronic acid trimer.

Workup

  1. stirringstirred for 18 hours at room temperature
  2. stirringThis mixture was stirred for 10 minutes
  3. customseparated into an aqueous fraction
  4. concentrationThe organic fraction was concentrated
  5. customto provide a white paste
  6. customThe paste was dried under vacuum (100 mmHg) at ambient temperature with a nitrogen
  7. waitbleed for 2 days

Sources & evidence

ORD record
ord-4a1e773baaba4222bc334660f0e30e2e
Source dataset
uspto-grants-2002_08
Patent number
US06441189B1

Reaction notes

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