1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-{4-[2-(2-Cyclopentyl-4-methoxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-2-methyl-propionitrile

HRID 858648노트

반응식

HRID 858648 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>>[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

3

반응물 2

HCID 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 Mel (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, 8 H), 1.94–2.05 (m, 2 H), 2.18 (s, 3H), 2.64–2.73 (m, 3 H), 3.75 (s, 2 H), 5.17 (s, 1 H), 6.89–6.97 (m, 2 H), 7.35–7.40 (m, 1 H). MS (ESI): 386 (M+H).

후처리

  1. customfollowed by Mel (0.076 mL, 1.21 mmol) and reaction
  2. customThe reaction mixture was partitioned between 1N HCl and EtOAc
  3. customThe layers of the resulting reaction mixture
  4. customwere separated
  5. washthe organic layer was washed with brine (1×10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by flash column chromatography (20% EtOAc in Hexanes)

출처 및 근거

ORD 기록
ord-bf03e173fb344ae69a7bdaf3c24aaac8
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07148226B2

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