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 2279837노트

반응식

HRID 2279837 반응식
[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

참가 물질

6

반응물 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-pyrazole2회HCID 178418918HCID 178418918, 화합물

생성물 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-pyrazole수율 100%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f17e3864940b4f6caf83f27bc54af478
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133224B2

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