Diisopropylamine → methyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-benzimidazol-7-yl]-3-hydroxy-2-(2-thienyl)methylpropanoate

HRID 487193노트

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HRID 487193 반응식
C([Li])CCC.C(NC(C)C)(C)C.[S:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21].[CH2:24]([C:28]1[N:32]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[Cl:40])[C:31]2[C:41]([CH:45]=[O:46])=[CH:42][CH:43]=[CH:44][C:30]=2[N:29]=1)[CH2:25][CH2:26][CH3:27]>O1CCCC1>[CH2:24]([C:28]1[N:32]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[Cl:40])[C:31]2[C:41]([CH:45]([OH:46])[CH:19]([CH2:18][C:14]3[S:13][CH:17]=[CH:16][CH:15]=3)[C:20]([O:22][CH3:23])=[O:21])=[CH:42][CH:43]=[CH:44][C:30]=2[N:29]=1)[CH2:25][CH2:26][CH3:27]

참가 물질

6

반응물 4

HCID 7912DiisopropylamineHCID 566367Methyl 3-(thiophen-2-yl)propanoateHCID 190942612-n-butyl-1-(2-chlorophenyl)methyl-1H-benzimidazole-7-carboxaldehydeHCID 178418339Butyllithium

생성물 1

HCID 19094218methyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-benzimidazol-7-yl]-3-hydroxy-2-(2-thienyl)methylpropanoate수율 56.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
-78 °C

실험 절차

A solution of n-butyl lithium (0.4 mL of 2.5M in hexane, 1 mmol) in dry tetrahydrofuran (5 mL) at -78° C. under argon was treated with diisopropylamine (108 mg, 1.06 mmol). This mixture was stirred 10 minutes at -78° C. and methyl 3-(2-thienyl)propanoate (156 mg, 0.92 mmol) was added in tetrahydrofuran. After being stirred an additional 30 minutes at -78° C., a solution of 2-n-butyl-1-(2-chlorophenyl)methyl-1H-benzimidazole-7-carboxaldehyde (200 mg, 0.61 mmol) in tetrahydrofuran (1.5 mL) was added. This mixture was stirred at -78° C. for 15 minutes and the reaction was quenched with saturated ammonium chloride. The product was extracted into ethyl acetate, washed with water, dried and concentrated product was flash chromatographed over silica gel with 5-10% of methanol in ethyl acetate to provide 0.17 g (56%) of methyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-benzimidazol-7-yl]-3-hydroxy-2-(2-thienyl)methylpropanoate as an oil.

후처리

  1. stirringAfter being stirred an additional 30 minutes at -78° C.
  2. stirringThis mixture was stirred at -78° C. for 15 minutes
  3. customthe reaction was quenched with saturated ammonium chloride
  4. extractionThe product was extracted into ethyl acetate
  5. washwashed with water
  6. customdried
  7. customchromatographed over silica gel with 5-10% of methanol in ethyl acetate

출처 및 근거

ORD 기록
ord-58fd245b859049c7bf7c01cc1420c5a2
출처 데이터셋
uspto-grants-1994_03
특허 번호
US05294631

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