2-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 1-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 16018

Reaction equation

HRID 16018 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:6]=1.C([Mg]Cl)(C)C.CO[B:23]1[O:27][C:26]([CH3:29])([CH3:28])[C:25]([CH3:31])([CH3:30])[O:24]1>C1COCC1>[O:11]1[CH2:12][CH2:13][CH2:14][CH2:15][CH:10]1[O:9][CH2:8][CH2:7][N:5]1[CH:6]=[C:2]([B:23]2[O:27][C:26]([CH3:29])([CH3:28])[C:25]([CH3:31])([CH3:30])[O:24]2)[CH:3]=[N:4]1

Participants

5

Reactant 3

HCID 109757592-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 593418524-Iodo-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-pyrazoleHCID 178418918HCID 178418918, compound

Product 1

HCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleYield 80.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazole (1.0 g, 3.1 mmol) in anhydrous THF (8 mL) was added iPrMgCl (2M in THF, 3.10 mL, 6.21 mmol) at 0° C. drop by drop under nitrogen. The reaction was stirred for 1 hour at 0° C. under nitrogen. To the solution was added 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.736 g, 4.66 mmoL) at 0° C. and the resulting yellow solution was allowed to stir for 1 hour at ambient temperature under nitrogen. The reaction was quenched with sat. aqueous solution of NH4Cl (10 mL). EtOAc (50 mL) and sat aqueous NH4Cl solution (10 mL) were added. The organic layer was separated, and the aqueous layer was extracted with EtOAc (3×50 mL), dried over Na2SO4, and concentrated to give the crude product as yellow oil. The oil was purified a silica gel column eluting with EtOAc and hexanes to provide 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole as clear oil (800 mgs, 80% yield). 1H NMR (300 MHz, DMSO-d6) δ 7.91 (s, 1H) 4.48-4.54 (m, 1H) 4.26-4.33 (m, 2H) 3.86-3.90 (m, 1H) 3.66-3.76 (m, 1H) 3.45-3.57 (m, 1H) 3.33-3.39 (m, 1H) 1.33-1.70 (m, 6H) 1.24 (s, 12H).

Workup

  1. stirringto stir for 1 hour at ambient temperature under nitrogen
  2. customThe reaction was quenched with sat. aqueous solution of NH4Cl (10 mL)
  3. additionwere added
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give the crude product as yellow oil
  9. customThe oil was purified a silica gel column
  10. washeluting with EtOAc and hexanes

Sources & evidence

ORD record
ord-9b0994932db2441089ec9ce62e502733
Source dataset
uspto-grants-2010_06
Patent number
US07732604B2

Linked notes

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