Methyl iodide → 2-{4-[2-(2-Cyclopentyl-4-methoxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-2-methyl-propionitrile

HRID 1453099노트

반응식

HRID 1453099 반응식
[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:26])([CH3:25])[C:23]#[N:24])=[C:18]([F:27])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:28]1CCN2C(=NCCC2)CC1.CI>>[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:26])[C:23]#[N:24])=[C:18]([F:27])[CH:17]=3)[CH2:11][C:10]([O:12][CH3:28])=[CH:9][C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

4

반응물 3

HCID 6328Methyl iodideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 587624232-{4-[2-(2-cyclopentyl-4,6-dioxotetrahydro-2H-pyran-2-yl)ethyl]-2-fluorophenyl)-2-methylpropanenitrile

생성물 1

HCID 587622442-{4-[2-(2-Cyclopentyl-4-methoxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-2-methyl-propionitrile수율 41%

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온도
0 °C

실험 절차

A magnetically stirring solution of 2-{4-[2-(2-cyclopentyl-4,6-dioxotetrahydro-2H-pyran-2-yl)ethyl]-2-fluorophenyl}-2-methylpropanenitrile (− rotation, 0.15 g, 0.40 mmol) was cooled to 0° C. DBU (0.18 mL, 1.21 mmol) was added followed by MeI (0.076 mL, 1.21 mmol) and reaction was stirred at 0° C. for 1 hour. The reaction mixture was partitioned between 1N HCl and EtOAc. The layers of the resulting reaction mixture were separated and the organic layer was washed with brine (1×10 mL), then dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by flash column chromatography (20% EtOAc in Hexanes) to give the desired product as a yellow oil (0.062 g, 41%). 1H NMR (400 MHz, CDCl3): δ 1.18 (d, J=6.5 Hz, 3H), 1.40 (d, J=6.5 Hz, 3H), 1.50-1.78 (m, 8H), 1.94-2.05 (m, 2H), 2.18 (s, 3H), 2.64-2.73 (m, 3H), 3.75 (s, 2H), 5.17 (s, 1H), 6.89-6.97 (m, 2H), 7.35-7.40 (m, 1H). MS (ESI): 386 (M+H).

후처리

  1. customThe reaction mixture was partitioned between 1N HCl and EtOAc
  2. customThe layers of the resulting reaction mixture
  3. customwere separated
  4. washthe organic layer was washed with brine (1×10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by flash column chromatography (20% EtOAc in Hexanes)

출처 및 근거

ORD 기록
ord-c69eb2825c8947f4a0829573b2fc83d8
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07473790B2

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