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

HRID 487853ノート

反応式

HRID 487853 の反応式
[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

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 21978327HCID 21978327、化合物溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-656c3d3dd6a542b1b582f99b2c0a4a84
出典データセット
uspto-grants-1994_03
特許番号
US05298479

反応ノート

読み込み中…