Hydrochloric Acid → methyl (Z)-2-(difluoromethyl)-5-(3-hydroxy-1-oxo-2-propenyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate

HRID 256808노트

반응식

HRID 256808 반응식
[C:1]([C:4]1[C:5]([CH2:21][CH:22]([CH3:24])[CH3:23])=[C:6]([C:17]([O:19][CH3:20])=[O:18])[C:7]([CH:14]([F:16])[F:15])=[N:8][C:9]=1[C:10]([F:13])([F:12])[F:11])(=[O:3])[CH3:2].[CH:25](OC)=[O:26].C[O-].[Na+].Cl>CCOCC.CO.O.CC(C)=O.N1C=CC=CC=1>[F:15][CH:14]([F:16])[C:7]1[C:6]([C:17]([O:19][CH3:20])=[O:18])=[C:5]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:4]([C:1](=[O:3])/[CH:2]=[CH:25]\[OH:26])=[C:9]([C:10]([F:12])([F:13])[F:11])[N:8]=1

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 7865Methyl formateHCID 10942334Sodium MethoxideHCID 20098194Methyl 5-acetyl-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate

생성물 1

HCID 86747352methyl (Z)-2-(difluoromethyl)-5-(3-hydroxy-1-oxo-2-propenyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate수율 52.6%

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 3283Diethyl Ether용매HCID 21978327HCID 21978327, 화합물용매

실험 절차

This example illustrates the preparation of Compound Numbers 23 and 24, an example of the acylation of a pyridine methyl ketone, followed by further derivation to compounds of the present invention. To methyl 5-acetyl-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (Compound No. 4, prepared as in Example A) (10.8 g, 30 mmol) in anhydrous ether (100 mL) were added methyl formate (3 g) and 25% sodium methoxide in methanol (10 g) (Aldrich), and the resulting mixture was stirred overnight. It was then poured into iced water, acidified with conc. HCl, and extracted with methylene chloride. The organic extract was washed with water and brine, dried (MgSO4), and conc. in vacuo. The residue was purified by flash chromatography with 20% ethyl acetate/cyclohexane to yield 6 g methyl (Z)-2-(difluoromethyl)-5-(3-hydroxy-1-oxo-2-propenyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (Compound No. 23) as a viscous red oil, a yield of 52.6%. nD25 1.4857.

후처리

  1. customthe preparation of Compound Numbers 23 and 24
  2. extractionextracted with methylene chloride
  3. extractionThe organic extract
  4. washwas washed with water and brine
  5. dry with materialdried (MgSO4)
  6. customThe residue was purified by flash chromatography with 20% ethyl acetate/cyclohexane

출처 및 근거

ORD 기록
ord-82d1dff2af09469b949922dac4b34280
출처 데이터셋
uspto-grants-1993_11
특허 번호
US05260262

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