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 2279837ノート

反応式

HRID 2279837 の反応式
[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

参加物

6

反応物 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 回HCID 178418918HCID 178418918、化合物

生成物 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-pyrazole収率 100%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f17e3864940b4f6caf83f27bc54af478
出典データセット
uspto-grants-2015_09
特許番号
US09133224B2

反応ノート

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