Hydrochloric Acid → (2-Fluoro-4-methoxyphenyl)boronic acid

HRID 51025Notes

Reaction equation

HRID 51025 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=1[F:15].C[O:17][B:18](OC)[O:19]C.Cl>C1COCC1>[F:15][C:8]1[CH:9]=[C:10]([O:13][CH3:14])[CH:11]=[CH:12][C:7]=1[B:18]([OH:19])[OH:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 37184441-Bromo-2-fluoro-4-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 15789384(2-Fluoro-4-methoxyphenyl)boronic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyllithium (1.6 M solution in hexanes, 29.1 mmol, 18.2 mL) was added to 1-bromo-2-fluoro-4-methoxybenzene (24.4 mmol, 5.0 g) in THF (150 mL) at −78° C. under an atmosphere of nitrogen. After stirring for thirty minutes the trimethylborate (95.1 mmol, 10.8 mL) was added over twenty minutes. The reaction was allowed to warm to room temperature overnight while stirring. The solution was then acidified with HCl (3 M, 200 mL), and extracted into EtOAc. The EtOAc was then extracted with NaOH (1 N, 4×100 mL), which was subsequently acidified with concentrated HCl forming (2-fluoro-4-methoxyphenyl)boronic acid as a white precipitate. The white precipitate (2.04 g, 49%) was filtered and dried. 1H NMR (CD3OD, 300 MHz): 7.29 (1H, t, J 8.0 Hz), 6.73 (1H, dd, J 8.5 and 2.2 Hz), 6.62 (1H, dd, J 11.4 and 2.2 Hz), 3.78 (3H, s.)

Workup

  1. additionwas added over twenty minutes
  2. extractionextracted into EtOAc
  3. extractionThe EtOAc was then extracted with NaOH (1 N, 4×100 mL), which

Sources & evidence

ORD record
ord-01ae091cd9b9499088d05622dec3bae5
Source dataset
uspto-grants-2004_03
Patent number
US06713471B1

Reaction notes

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