Thiophene → Ethyl (E)-4-[2-(5,5-dimethyl-8-(2-thienyl)-5,6-dihydronaphthalen-2-yl)ethenyl]-benzoate

HRID 24569

반응식

HRID 24569 반응식
[S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li:10])CCC.[CH3:11][C:12]1([CH3:43])[CH2:21][CH:20]=[C:19](OS(C(F)(F)F)(=O)=O)[C:18]2[CH:17]=[C:16](/[CH:30]=[CH:31]/[C:32]3[CH:42]=[CH:41][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][CH:33]=3)[CH:15]=[CH:14][C:13]1=2>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Li:10][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1.[CH3:43][C:12]1([CH3:11])[CH2:21][CH:20]=[C:19]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[C:18]2[CH:17]=[C:16](/[CH:30]=[CH:31]/[C:32]3[CH:33]=[CH:34][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:41][CH:42]=3)[CH:15]=[CH:14][C:13]1=2

참가 물질

8

반응물 3

HCID 8030ThiopheneHCID 19695065ethyl (E)-4-[2-(5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-5,6-dihydronaphthalen-2-yl)ethenyl]benzoateHCID 178418339Butyllithium

생성물 2

HCID 15887383Ethyl (E)-4-[2-(5,5-dimethyl-8-(2-thienyl)-5,6-dihydronaphthalen-2-yl)ethenyl]-benzoateHCID 178418439HCID 178418439, 화합물

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

A solution of lithiothiophene was prepared by the addition of 0.10 g (0.095 mL, 1.2 mmol) of thiophene to a cold solution (−78° C.) of 0.61 g (0.90 mL, 1.4 mmol, 1.6 M in hexanes) of n-butyl lithium in 2.0 mL of tetrahydrofuran. The solution was stirred at −78° C. for 35 min and then a solution of 0.158 g (1.2 mmol) of zinc chloride in 2.0 mL of tetrahydrofuran was added. The resulting solution was stirred at −78° C. to room temperature for 1 h and then the organozinc was added via cannula to a mixture of 0.212 g (0.44 mmol) of ethyl (E)-4-[2-(5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-5,6-dihydronaphthalen-2-l)ethenyl] benzoate (Compound A9) and 18 mg (0.016 mmol) of tetrakis(triphenylphosphine)palladium(0) in 2.0 mL of tetrahydrofuran. The resulting mixture was stirred at room temperature for 10 min and then heated at 50° C. for 1 h. The reaction was quenched by the addition of sat. aqueous NH4Cl. The mixture was extracted with EtOAc (2×), and washed with brine. The organic phase was dried over Na2SO4 and then concentrated in vacuo. The crude material product was purified by flash chromatography (silica, 15% ethyl acetate in hexanes) to afford the title compound as a solid.

후처리

  1. stirringThe resulting solution was stirred at −78° C. to room temperature for 1 h
  2. stirringThe resulting mixture was stirred at room temperature for 10 min
  3. temperatureheated at 50° C. for 1 h
  4. customThe reaction was quenched by the addition of sat. aqueous NH4Cl
  5. extractionThe mixture was extracted with EtOAc (2×)
  6. washwashed with brine
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material product was purified by flash chromatography (silica, 15% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-4ce7c23667ed4c469af66e055671ecc8
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06855832B2

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