Diisopropylamine → 2-Chloro-alpha-(3-methoxyphenyl)-3-pyridinemethanol

HRID 852088

반응식

HRID 852088 반응식
C([Li])CCC.C(NC(C)C)(C)C.C([N-]C(C)C)(C)C.[Li+].[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.[CH:28](=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1.[Cl-].[NH4+]>CCCCCC.O1CCCC1.O>[Cl:21][C:22]1[C:27]([CH:28]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=2)[OH:37])=[CH:26][CH:25]=[CH:24][N:23]=1

참가 물질

10

반응물 6

HCID 7912DiisopropylamineHCID 79772-ChloropyridineHCID 115693-MethoxybenzaldehydeHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

생성물 1

HCID 201457332-Chloro-alpha-(3-methoxyphenyl)-3-pyridinemethanol수율 51%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회HCID 8058Hexane용매

실험 절차

Combine 2.5 M n-butyl lithium in hexane (40 mL), diisopropyl amine (14 mL, 0.10 mol) and cold (−68° C.) tetrahydrofuran (250 mL) and stir for 20 minutes, to generate lithium diisopropylamide. Add 2-chloro-pyridine (9.5 mL, 0.10 mol) dissolved in tetrahydrofuran (10 mL) and stir for 45 minutes. Add m-anisaldehyde (13.6 g, 0.10 mol) in 10 mL tetrahydrofuran, stir for 45 minutes and let warm to room temperature over the weekend. Pour reaction mixture into water, add saturated ammonium chloride (50 mL), separate and dry. Extract with ether (twice), wash combined aqueous layers with saturated sodium chloride, dry, evaporate and purify by flash (silica) chromatography using a graded solvent mixture of dichloromethane to 10% ethyl acetate in dichloromethane to give the title compound as an oil (12.74 g, 51% Yield). NMR agrees with the final, desired compound.

후처리

  1. additionPour
  2. customseparate
  3. customdry
  4. extractionExtract with ether (twice),
  5. washwash
  6. customdry
  7. customevaporate
  8. custompurify by flash (silica) chromatography
  9. additiona graded solvent mixture of dichloromethane to 10% ethyl acetate in dichloromethane

출처 및 근거

ORD 기록
ord-0b4136e69fa14d5aabb9d73c5cf3a4d0
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07253165B2

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