1-碘-3,3,3-三氟丙烷 → 2-Isopropyl-3,6-dimethoxy-5-(3,3,3-trifluoro-propyl)-2,5-dihydro-pyrazine

HRID 72016笔记

反应方程式

HRID 72016 反应方程式
[CH:1]([CH:4]1[C:9]([O:10][CH3:11])=[N:8][CH2:7][C:6]([O:12][CH3:13])=[N:5]1)([CH3:3])[CH3:2].C([Li])CCC.I[CH2:20][CH2:21][C:22]([F:25])([F:24])[F:23]>C1COCC1.C(OCC)(=O)C>[CH:1]([CH:4]1[C:9]([O:10][CH3:11])=[N:8][CH:7]([CH2:20][CH2:21][C:22]([F:25])([F:24])[F:23])[C:6]([O:12][CH3:13])=[N:5]1)([CH3:3])[CH3:2]

参与物

6

反应物 3

HCID 1561651-碘-3,3,3-三氟丙烷HCID 38009092-异丙基-3,6-二甲氧基-2,5-二氢吡嗪HCID 178418339正丁基锂

产物 1

HCID 666212022-Isopropyl-3,6-dimethoxy-5-(3,3,3-trifluoro-propyl)-2,5-dihydro-pyrazine收率 59%

试剂、催化剂与溶剂 2

HCID 8028四氢呋喃溶剂2 次HCID 8857乙酸乙酯溶剂

反应条件

温度
-78 °C

实验过程

To a stirred solution of 2-isopropyl-3,6-dimethoxy-2,5-dihydro-pyrazine (1 mL, 5.58 mmol) in THF (13.5 mL) under argon at −78° C. was added a solution of n-butyllithium (2.5 M, 2.3 mL, 5.75 mmol). The solution was stirred at −78° C. for 30 minutes. A solution of 1-Iodo-3,3,3-trifluoropropane (925 μL, 5.87 mmol) in THF (11.5 mL) was added slowly. The resulting solution was stirred at −78° C. for 5 hours, warmed to room temperature and diluted with ethyl acetate. The organic layer was washed successively with saturated aqueous NH4Cl solution, water and brine. The organic layer was then dried (MgSO4), concentrated and purified by flash chromatography to yield 2-Isopropyl-3,6-dimethoxy-5-(3,3,3-trifluoro-propyl)-2,5-dihydro-pyrazine (915 mg, 59%). 1H-NMR: 400 MHz, (CDCl3) δ: 4.04-3.99 (m, 1H), 3.98-3.95 (m, 1H), 3.71 (s, 3H), 3.68 (s, 3H), 2.29-2.20 (m, 1H), 2.18-2.04 (m, 3H), 1.94-1.84 (m, 1H), 1.03 (d, J=6.9 Hz, 3H), 0.71 (d, J=6.8 Hz, 3H) ppm.

后处理

  1. stirringThe resulting solution was stirred at −78° C. for 5 hours
  2. temperaturewarmed to room temperature
  3. washThe organic layer was washed successively with saturated aqueous NH4Cl solution, water and brine
  4. dry with materialThe organic layer was then dried (MgSO4)
  5. concentrationconcentrated
  6. custompurified by flash chromatography

来源与证据

ORD记录
ord-4592428f9e3e4f18a748d35f8cca370d
来源数据集
uspto-grants-2014_09
专利号
US08822430B2

反应笔记

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