Lithium Chloride → 1-[2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 2279837Notes

Reaction equation

HRID 2279837 reaction equation
[CH3:1][C:2]([CH3:18])([CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[CH2:3][N:4]1[CH:8]=[C:7](I)[CH:6]=[N:5]1.C([Mg]Cl)(C)C.[Li+].[Cl-].CO[B:28]1[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]1>C1COCC1>[CH3:1][C:2]([CH3:18])([CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[CH2:3][N:4]1[CH:8]=[C:7]([B:28]2[O:32][C:31]([CH3:34])([CH3:33])[C:30]([CH3:36])([CH3:35])[O:29]2)[CH:6]=[N:5]1

Participants

6

Reactant 4

HCID 433294Lithium ChlorideHCID 109757592-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 866977771-[2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl]-4-iodo-1H-pyrazole2×HCID 178418918HCID 178418918, compound

Product 1

HCID 866977761-[2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-[2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl]-4-iodo-1H-pyrazole (Compound 47D, 539 mg, 1.48 mmol) in THF (20 mL) was added 1.3 M of i-PrMgCl.LiCl in THF (2.28 mL, 2.96 mmol) at 0° C. The reaction was allowed to warm gradually to rt over 20 min. 2-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.73 mL, 4.44 mmol) was added and the mixture was stirred at rt for 16 hrs. The reaction mixture was quenched with water and then extracted with EtOAc. The organic layer was washed with water, brine (2×), dried over sodium sulfate, filtered, concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [0-40% Acetone/Heptanes] to afford 500 mg the desired product (100%). 1H NMR (400 MHz, CD3OD) δ 7.81 (s, 1H), 7.65 (s, 1H), 4.58 (d, J=2.8 Hz, 1H), 4.14 (s, 2H), 3.80-3.91 (m, 1H), 3.46-3.54 (m, 1H), 3.44 (d, J=9.6 Hz, 1H), 3.02 (d, J=9.3 Hz, 1H), 1.80-1.97 (m, 1H), 1.68-1.79 (m, 1H), 1.49-1.67 (m, 5H), 1.31 (s, 10H), 0.87-0.98 (m, 6H), 0.84-1.01 (m, 1H). MS (ESI): m/z=365.51 [M+H]+. UPLC: tR=1.54 min (UPLC-TOF: polar—2 min).

Workup

  1. customat 0° C
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with water, brine (2×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified

Sources & evidence

ORD record
ord-f17e3864940b4f6caf83f27bc54af478
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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