Lithium Hexamethyldisilazide → Methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutanecarboxylate

HRID 1930134Notes

Reaction equation

HRID 1930134 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:12][CH2:13][CH2:14][CH:15]([C:20]1[CH:25]=[CH:24][C:23]([B:26]2[O:30][C:29]([CH3:32])([CH3:31])[C:28]([CH3:34])([CH3:33])[O:27]2)=[C:22]([Cl:35])[CH:21]=1)[C:16]([O:18][CH3:19])=[O:17]>C1COCC1>[Cl:35][C:22]1[CH:21]=[C:20]([C:15]2([C:16]([O:18][CH3:19])=[O:17])[CH2:14][CH2:13][CH2:12]2)[CH:25]=[CH:24][C:23]=1[B:26]1[O:30][C:29]([CH3:32])([CH3:31])[C:28]([CH3:34])([CH3:33])[O:27]1

Participants

4

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 59627651Methyl 5-bromo-2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanoate2×

Product 1

HCID 59627692Methyl 1-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutanecarboxylateYield 98.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Lithium bis(trimethylsilyl)amide (0.872 mL, 0.87 mmol) was added dropwise to methyl 5-bromo-2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanoate (Intermediate 7-3; 342 mg, 0.79 mmol) in THF (10 mL) cooled to 0° C. under nitrogen the reaction and was stirred at 0° C. for 12 hours. 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)cyclobutanecarboxylate (273 mg, 98%) as a colourless gum.

Workup

  1. customthe reaction
  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-95c714dc4a2c4adaabb6d949be56cb73
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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