Ethyl 3-iodobenzoate → ethyl 3-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)benzoate

HRID 1876922노트

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HRID 1876922 반응식
I[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].C([Mg]Cl)(C)C.[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[CH:27][N:28]3[C:37]=2[CH:36]=[C:35]2[C@@:30]([CH3:40])([C@@H:31]([CH:38]=[O:39])[CH2:32][CH2:33][CH2:34]2)[CH2:29]3)=[CH:21][CH:20]=1>C1COCC1>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[CH:27][N:28]3[C:37]=2[CH:36]=[C:35]2[C@@:30]([CH3:40])([C@@H:31]([CH:38]([OH:39])[C:2]4[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=4)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:32][CH2:33][CH2:34]2)[CH2:29]3)=[CH:21][CH:20]=1

참가 물질

5

반응물 3

HCID 143542Ethyl 3-iodobenzoateHCID 46180541(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehydeHCID 178418918HCID 178418918, 화합물

생성물 1

HCID 67447028ethyl 3-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)benzoate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred solution of ethyl 3-iodobenzoate (0.17 mL, 1 mmol) in anhydrous THF (2 mL) cooled in an acetonitrile-dry ice bath was added isopropylmagnesium chloride solution (2M in THF, 0.5 mL, 1 mmol) dropwise under nitrogen. The reaction mixture was stirred at the same temperature for 30 min before (5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehyde (Example 1g, 55 mg, 0.18 mmol) was added. The mixture was stirred in an acetonitrile-dry ice bath for 1 hr before being quenched by the addition of saturated aqueous ammonium chloride solution (3 mL) at the same temperature. The reaction mixture was extracted with ethyl acetate (3×3 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Silica gel flash chromatography (25-100% ethyl acetate in heptanes, then 0-10% methanol in ethyl acetate) gave ethyl 3-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)benzoate as a solid.

후처리

  1. additionwas added
  2. custombefore being quenched by the addition of saturated aqueous ammonium chloride solution (3 mL) at the same temperature
  3. extractionThe reaction mixture was extracted with ethyl acetate (3×3 mL)
  4. dry with materialThe combined organic solutions were dried (Na2SO4)
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-107733c00e694e678dc639f37e52e0a0
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309730B2

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