Hydrochloric Acid → (4-(1-Hydroxycyclopropyl)phenyl)boronic acid

HRID 1041942Notes

Reaction equation

HRID 1041942 reaction equation
[CH2:1]([Mg]Br)[CH3:2].CO[C:7](=[O:23])[C:8]1[CH:13]=[CH:12][C:11]([B:14]2[O:18]C(C)(C)C(C)(C)[O:15]2)=[CH:10][CH:9]=1.Cl>C(OCC)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[OH:23][C:7]1([C:8]2[CH:9]=[CH:10][C:11]([B:14]([OH:15])[OH:18])=[CH:12][CH:13]=2)[CH2:2][CH2:1]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 2773500Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 178418443HCID 178418443, compound

Product 1

HCID 57416393(4-(1-Hydroxycyclopropyl)phenyl)boronic acid

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 3.0 M solution of ethylmagnesium bromide in diethylether (7.6 mL) is added to a stirred solution of titanium(IV) isopropoxide (2.2 mL) in diethylether (70 mL) chilled to −78° C. The resultant solution is stirred at −78° C. for 1.5 h, before 4-(4,4,5,5-tetramethyl-[1,3,2]dioxa borolan-2-yl)-benzoic acid methyl ester (2.0 g) is added. The reaction mixture is warmed to ambient temperature and stirred for an additional 12 h. Then, 1 M aqueous hydrochloric acid is added and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are dried (sodium sulphate) and the solvent is evaporated. The residue is dissolved in acetone (60 mL) and 0.1 M aqueous NH4OAc solution (50 mL) followed by NaIO4 (2.3 g) is added. The resulting reaction mixture is stirred at room temperature for 18 h. After removal of the acetone, the residue is extracted with ethyl acetate. The combined extracts are dried (sodium sulphate) and the solvent is evaporated. The residue is purified by chromatography on silicagel (cyclohexane/ethyl acetate).

Workup

  1. additionis added
  2. temperatureThe reaction mixture is warmed to ambient temperature
  3. extractionthe resulting mixture is extracted with ethyl acetate
  4. dry with materialThe combined organic extracts are dried (sodium sulphate)
  5. customthe solvent is evaporated
  6. dissolutionThe residue is dissolved in acetone (60 mL)
  7. additionis added
  8. customThe resulting reaction mixture
  9. stirringis stirred at room temperature for 18 h
  10. customAfter removal of the acetone
  11. extractionthe residue is extracted with ethyl acetate
  12. dry with materialThe combined extracts are dried (sodium sulphate)
  13. customthe solvent is evaporated
  14. customThe residue is purified by chromatography on silicagel (cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-e4d709af50194d6f9bb84e7211db1e33
Source dataset
uspto-grants-2013_10
Patent number
US08557782B2

Reaction notes

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