1,2-Dibromoethane → Methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropane-1-carboxylate

HRID 1930142Notes

Reaction equation

HRID 1930142 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:11][C:12]1[CH:13]=[C:14]([CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH:15]=[CH:16][C:17]=1[B:18]1[O:22][C:21]([CH3:24])([CH3:23])[C:20]([CH3:26])([CH3:25])[O:19]1.Br[CH2:33][CH2:34]Br>C1COCC1>[Cl:11][C:12]1[CH:13]=[C:14]([C:27]2([C:28]([O:30][CH3:31])=[O:29])[CH2:34][CH2:33]2)[CH:15]=[CH:16][C:17]=1[B:18]1[O:22][C:21]([CH3:23])([CH3:24])[C:20]([CH3:25])([CH3:26])[O:19]1

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 2733832Lithium HexamethyldisilazideHCID 58464478Benzeneacetic acid, 3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-, methyl ester

Product 1

HCID 59627717Methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropane-1-carboxylateYield 16.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Lithium bis(trimethylsilyl)amide (7.08 mL, 7.08 mmol) was added dropwise to methyl 2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate (1 g, 3.22 mmol) in THF (20 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 30 minutes and then 1,2-dibromoethane (0.305 mL, 3.54 mmol) was added to the reaction and was stirred at 0° C. for 5 minutes. The reaction mixture was quenched with saturated NH4Cl (50 mL) and was diluted with EtOAc (75 mL). The organic layer was separated and re-extracted with EtOAc (75 mL). The combined organics were washed with saturated brine (50 mL), dried (MgSO4), filtered and concentrated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (0.182 g, 16.79%) as a colourless gum.

Workup

  1. stirringwas stirred at 0° C. for 5 minutes
  2. customThe reaction mixture was quenched with saturated NH4Cl (50 mL)
  3. additionwas diluted with EtOAc (75 mL)
  4. customThe organic layer was separated
  5. extractionre-extracted with EtOAc (75 mL)
  6. washThe combined organics were washed with saturated brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford crude product
  11. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane
  12. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-aca28f8174904daf9dbf40873bdfce0a
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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