Trimethyl borate → 3-(2,4-Dioxobicyclo[3.2.1]oct-3-yl)-4-ethylphenylboronic acid

HRID 72266Notes

Reaction equation

HRID 72266 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6](I)=[CH:5][C:4]=1[CH:10]1[C:16](=[O:17])[CH:15]2[CH2:18][CH:12]([CH2:13][CH2:14]2)[C:11]1=[O:19])[CH3:2].[Cl-].[Li+].C([Mg]Cl)(C)C.[B:27](OC)([O:30]C)[O:28]C>O1CCCC1.ClCCl>[O:17]=[C:16]1[CH:10]([C:4]2[CH:5]=[C:6]([B:27]([OH:30])[OH:28])[CH:7]=[CH:8][C:3]=2[CH2:1][CH3:2])[C:11](=[O:19])[CH:12]2[CH2:18][CH:15]1[CH2:14][CH2:13]2

Participants

6

Reactant 3

HCID 8470Trimethyl borateHCID 684856003-(2-Ethyl-5-iodophenyl)bicyclo[3.2.1]octane-2,4-dioneHCID 178461733HCID 178461733, compound

Product 1

HCID 684806443-(2,4-Dioxobicyclo[3.2.1]oct-3-yl)-4-ethylphenylboronic acidYield 90.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-(2-ethyl-5-iodophenyl)bicyclo[3.2.1]octane-2,4-dione (0.65 g, 1.77 mmol) in anhydrous tetrahydrofuran (15 ml) at −10° C. is added iso-propyl magnesium chloride lithium chloride complex (10.6 ml, 10.6 mmol, 1M in tetrahydrofuran) dropwise over 10 minutes. The reaction mixture is stirred at this temperature for 1.5 hours, then cooled to −78° C., at which point trimethyl borate (1.39 ml, 12.4 mmol) is added dropwise to maintain a temperature below −60° C. After re-cooling to −78° C. the mixture is further stirred for 5 minutes, then additionally at room temperature for 1 hour. The solution is quenched with 2M hydrochloric acid and extracted with ethyl acetate (×3). All organic fractions are combined, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo to give an orange-coloured gum. This crude product is dissolved in a minimum amount of dichloromethane then precipitated with iso-hexane to afford 3-(2,4-dioxo-bicyclo[3.2.1]oct-3-yl)-4-ethylphenylboronic acid (0.46 g, 90%) as a cream-coloured solid.

Workup

  1. additionis added dropwise
  2. temperatureto maintain a temperature below −60° C
  3. stirringis further stirred for 5 minutes
  4. waitadditionally at room temperature for 1 hour
  5. customThe solution is quenched with 2M hydrochloric acid
  6. extractionextracted with ethyl acetate (×3)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated in vacuo
  10. customto give an orange-coloured gum
  11. customthen precipitated with iso-hexane

Sources & evidence

ORD record
ord-00797c4ca0064e7f94a00bee27fd3416
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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