Chlorotrimethylsilane → (5RS)-5-hydroxy-5-(2-iodo-3-methoxy-6-pyridyl)-pentanoic acid methyl ester

HRID 55278

반응식

HRID 55278 반응식
BrCCBr.Cl[Si](C)(C)C.[CH3:10][O:11][C:12](=[O:17])[CH2:13][CH:14](I)[CH3:15].[I-].COC(C(C)C[Zn+])=O.[Cl-].[Li+].[I:29][C:30]1[C:35]([O:36][CH3:37])=[CH:34][CH:33]=[C:32]([CH:38]=[O:39])[N:31]=1>O1CCCC1.ClCCl.[Cl-].[NH4+].[Zn].[Cu+]>[CH3:10][O:11][C:12](=[O:17])[CH2:13][CH2:14][CH2:15][CH:38]([OH:39])[C:32]1[N:31]=[C:30]([I:29])[C:35]([O:36][CH3:37])=[CH:34][CH:33]=1

참가 물질

12

반응물 6

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 433294Lithium ChlorideHCID 132118643-Iodobutyric acid methyl esterHCID 199574546-Iodo-5-methoxypicolinaldehydeHCID 178500474HCID 178500474, 화합물

생성물 1

HCID 54350032(5RS)-5-hydroxy-5-(2-iodo-3-methoxy-6-pyridyl)-pentanoic acid methyl ester수율 72.7%

시약·촉매·용매 5

HCID 23994Zinc촉매2회HCID 104815Copper(1+)촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매4회HCID 25517Ammonium Chloride용매

반응 조건

온도
25 °C

실험 절차

680 mg of zinc foil cut into small sections (Aldrich 0.25 mm thickness, 99.999%) in 1 ml of absolute tetrahydrofuran is heated to 65° C. with 80 mg of 1,2-dibromoethane for 1 minute, cooled to 25° C., mixed with 40 μl of chlorotrimethylsilane and stirred for 15 minutes. A solution of 2.3 g of 3-iodobutyric acid methyl ester in 5 ml of absolute tetrahydrofuran is instilled in this activated zinc at 30° C., and the mixture is stirred for 16 hours at 35°-40° C. 4.3 ml of the thus obtained 2-methoxycarbonylpropylzinc iodide solution is instilled at -20° C. in a solution of 430 mg of copper(I) dyanid and 430 mg of lithium chloride in 1 ml of tetrahydrofuran. The reaction mixture is stirred for 5 minutes at 0° C., cooled again to -20° C., mixed with a solution of 1.1 g of 2-iodo-3-methoxypyridine-6-aldehyde in 2 ml of tetrahydrofuran and 2 ml of dichloromethane and 1.9 ml of boron trifluoride-ethyl ether complex, stirred for three hours at 0° C. and 20 hours at room temperature. The reaction mixture is poured in saturated ammonium chloride solution, the precipitate is suctioned off on diatomaceous earth, the filter residue is washed with ethyl acetate, the organic phase is separated and the water phase is also shaken out three times with ethyl acetate. The organic phase is dried on sodium sulfate, concentrated by evaporation and the crude product is chromatographed on silica gel with hexane/0-20% ethyl acetate. 1.11 g of (5RS)-5-hydroxy-5-(2-iodo-3-methoxy-6-pyridyl)-pentanoic acid methyl ester is obtained as oil.

후처리

  1. stirringthe mixture is stirred for 16 hours at 35°-40° C
  2. stirringThe reaction mixture is stirred for 5 minutes at 0° C.
  3. temperaturecooled again to -20° C.
  4. stirringstirred for three hours at 0° C. and 20 hours at room temperature
  5. washthe filter residue is washed with ethyl acetate
  6. customthe organic phase is separated
  7. stirringthe water phase is also shaken out three times with ethyl acetate
  8. customThe organic phase is dried on sodium sulfate
  9. concentrationconcentrated by evaporation
  10. customthe crude product is chromatographed on silica gel with hexane/0-20% ethyl acetate

출처 및 근거

ORD 기록
ord-bddae5e50ef44f10a4e607843a73c5c1
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05624943

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