Ethyl 1-(4-bromo-2-iodobenzyl)-4-(trifluoromethyl)cyclohexanecarboxylate → 6'-Bromo-4-(trifluoromethyl)spiro[cyclohexane-1,2'-inden]-1'(3'H)-one

HRID 1770919노트

반응식

HRID 1770919 반응식
[Br:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2([C:17](OCC)=[O:18])[CH2:12][CH2:11][CH:10]([C:13]([F:16])([F:15])[F:14])[CH2:9][CH2:8]2)=[C:4](I)[CH:3]=1.C([Mg]Cl)(C)C.[Cl-].[Li+]>C1COCC1>[Br:1][C:2]1[CH:23]=[C:22]2[C:5]([CH2:6][C:7]3([CH2:12][CH2:11][CH:10]([C:13]([F:15])([F:14])[F:16])[CH2:9][CH2:8]3)[C:17]2=[O:18])=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 67979570Ethyl 1-(4-bromo-2-iodobenzyl)-4-(trifluoromethyl)cyclohexanecarboxylate2회HCID 178461733HCID 178461733, 화합물

생성물 1

HCID 679795566'-Bromo-4-(trifluoromethyl)spiro[cyclohexane-1,2'-inden]-1'(3'H)-one수율 52.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

Ethyl 1-(4-bromo-2-iodobenzyl)-4-(trifluoromethyl)cyclohexanecarboxylate (Intermediate 77, 2.41 g, 4.64 mmol) was dissolved in THF (40 mL). The atmosphere was exchanged to argon, and the solution was cooled to −78° C. Isopropylmagnesium chloride—lithium chloride (1.3 M in THF) (2.86 mL, 3.71 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 15 min. The reaction mixture left to warm up to r.t., while stirred for 30 min. The reaction mixture was quenched with sat. NH4Cl. Brine was added, and the phases were separated. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by preparative chromatography (XBridge C18 (10 μm, 50×250 mm) column with a gradient of 50-100% MeCN) in (95% 0.05M NH4OAc in MilliQ water and 5% MeCN) over 15 min at a flow rate of 100 mL/min). The purification provided the title compound (0.849 g, 52% yield): 1H NMR (400 MHz, CDCl3) δ ppm 1.51-1.61 (m, 3H) 1.75-1.84 (m, 2H) 1.97 (m, 2H) 2.18 (m, 2H) 2.90 (s, 2H) 7.29 (dd, 1H) 7.69 (dd, 1H) 7.84 (d, 1H); MS (ES+) 346 [M+H]+.

후처리

  1. waitThe reaction mixture left
  2. temperatureto warm up to r.t.
  3. stirringwhile stirred for 30 min
  4. customThe reaction mixture was quenched with sat. NH4Cl
  5. additionBrine was added
  6. customthe phases were separated
  7. washThe organic layer was washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by preparative chromatography (XBridge C18 (10 μm, 50×250 mm) column with a gradient of 50-100% MeCN) in (95% 0.05M NH4OAc in MilliQ water and 5% MeCN) over 15 min at a flow rate of 100 mL/min)
  12. customThe purification

출처 및 근거

ORD 기록
ord-227329e091c744de988822738d744cc1
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09248129B2

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