Trimethyl borate → 3,5-Difluoro-2-methylsulfanylphenylboronic acid

HRID 1513934Notes

Reaction equation

HRID 1513934 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]([F:14])[C:8]=1[S:15][CH3:16].C[O:18][B:19](OC)[O:20]C>O1CCCC1>[F:14][C:9]1[C:8]([S:15][CH3:16])=[C:7]([B:19]([OH:20])[OH:18])[CH:12]=[C:11]([F:13])[CH:10]=1

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 670051631-Bromo-3,5-difluoro-2-methylsulfanylbenzeneHCID 178418918HCID 178418918, compound

Product 1

HCID 575525453,5-Difluoro-2-methylsulfanylphenylboronic acidYield 61.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

Charge a flask with isopropyl magnesium chloride (145 mL, 2M in THF, 290 mmol) and dilute with tetrahydrofuran (150 mL) and heat to 40° C. under nitrogen. Add 1-bromo-3,5-difluoro-2-methylsulfanyl-benzene (28 g, 117 mmol) slowly over 5 minutes. After 30 minutes, cool the reaction to 0° C. and add trimethylborate (46 mL, 410 mmol) diluted with tetrahydrofuran (100 mL) via an addition funnel over 5 minutes. Partition the resulting gelatinous mixture between methylene chloride and 1N HCl. Acidify the aqueous layer to pH˜1 (if needed) and vigorously stir the biphasic mixture until all solids are dissolved. Separate the organic layer. Dry over sodium sulfate, filter and concentrate. Triturate with hexanes and filter to yield 14.7 g (61%) of the title compound.

Workup

  1. temperaturecool
  2. customthe reaction to 0° C.
  3. customPartition the resulting gelatinous mixture between methylene chloride and 1N HCl
  4. dissolutionare dissolved
  5. customSeparate the organic layer
  6. dry with materialDry over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate
  9. customTriturate with hexanes
  10. filtrationfilter

Sources & evidence

ORD record
ord-5b5f1cd02b7f40bcac7180954cd8d843
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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