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 2208142Notes

Reaction equation

HRID 2208142 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.b10 (27.51 g; 0.10 mol) in dry tert. butylmethylether (500 mL) is cooled to −20° C. before addition of n-butyl lithium (1.6M 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-a4070eb0fe9d482392b37ddcff930558
Source dataset
uspto-grants-2016_06
Patent number
US09376442B2

Reaction notes

Loading…