2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 2-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

HRID 2410945Notes

Reaction equation

HRID 2410945 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([F:10])=[CH:4][C:3]=1[O:11][CH2:12][CH:13]1[CH2:15][CH2:14]1.C([Li])CCC.C(O[B:25]1[O:29][C:28]([CH3:31])([CH3:30])[C:27]([CH3:33])([CH3:32])[O:26]1)(C)C>C(OC)(C)(C)C>[CH:13]1([CH2:12][O:11][C:3]2[CH:4]=[C:5]([F:10])[C:6]([O:8][CH3:9])=[CH:7][C:2]=2[B:25]2[O:29][C:28]([CH3:31])([CH3:30])[C:27]([CH3:33])([CH3:32])[O:26]2)[CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 668667661-Bromo-2-cyclopropylmethoxy-4-fluoro-5-methoxy-benzeneHCID 178418339Butyllithium

Product 1

HCID 668663772-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

A stirred solution of 1-bromo-2-cyclopropylmethoxy-4-fluoro-5-methoxy-benzene from example B.b7 (27.51 g; 0.10 mol) in dry tert. butylmethylether (500 mL) is cooled to −20° C. before addition of n-butyl lithium (1.6 M in hexane; 68.8 mL; 0.11 mol) via syringe. After complete addition stirring is continued for one hour. Neat 2-iso-propoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane is added via syringe into the reaction mixture at −40° C. After 30 min the reaction is quenched with 1M citric acid (200 mL) at 0° C. and stirred for one hour at ambient temperature. The organic layer is separated. The aqueous layer is extracted with tert. butylmethylether (100 mL). The combined organic layers are washed with brine (200 mL) dried over MgSO4 and filtered through a plug of neutral alumina containing 5 wt % of water. The product is completely eluted with several small portions of tert. butylmethylether. The solvent is removed under reduced pressure. The crude is purified by short path distillation at 3×10−3 mbar (160° C.) to give the title compound as a colorless oil that solidifies at ambient temperature.

Workup

  1. additionAfter complete addition
  2. customAfter 30 min the reaction is quenched with 1M citric acid (200 mL) at 0° C.
  3. stirringstirred for one hour at ambient temperature
  4. customThe organic layer is separated
  5. extractionThe aqueous layer is extracted with tert. butylmethylether (100 mL)
  6. washThe combined organic layers are washed with brine (200 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered through a plug of neutral alumina containing 5 wt % of water
  9. washThe product is completely eluted with several small portions of tert. butylmethylether
  10. customThe solvent is removed under reduced pressure
  11. distillationThe crude is purified by short path distillation at 3×10−3 mbar (160° C.)

Sources & evidence

ORD record
ord-ae25c28bd2ad494981398e7c27bf8a6e
Source dataset
uspto-grants-2014_08
Patent number
US08816085B2

Reaction notes

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