Hydrochloric Acid → 3-{2-Methyl-4-[3-methyl-5-(2-pyridin-2-yl-4-trifluoromethyl-phenoxy)-phenoxy]-phenyl}-propionic acid

HRID 1822289ノート

反応式

HRID 1822289 の反応式
C([O:3][C:4](=[O:39])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[CH:17]=[C:16]([CH3:37])[CH:15]=2)=[CH:9][C:8]=1[CH3:38])C.[OH-].[Na+].Cl>C(O)C.O>[CH3:38][C:8]1[CH:9]=[C:10]([O:13][C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:29])([F:30])[F:28])=[CH:23][C:22]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[CH:17]=[C:16]([CH3:37])[CH:15]=2)[CH:11]=[CH:12][C:7]=1[CH2:6][CH2:5][C:4]([OH:39])=[O:3]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 690795633-{2-Methyl-4-[3-methyl-5-(2-pyridin-2-yl-4-trifluoromethyl-phenoxy)-phenoxy]-phenyl}-propionic acid ethyl ester

生成物 1

HCID 113296293-{2-Methyl-4-[3-methyl-5-(2-pyridin-2-yl-4-trifluoromethyl-phenoxy)-phenoxy]-phenyl}-propionic acid収率 38%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

A mixture of 3-{4-[3-(2-bromo-4-trifluoromethyl-phenoxy)-5-methyl-phenoxy]-2-methyl-phenyl}-propionic acid ethyl ester (0.155 g, 0.289 mmol) and 2-tributylstannyl pyridine (0.210 g, 0.571 mmol) in dry toluene (8 mL) is purged with N2 and then tetrakis(triphenylphospine)pallium (0) (0.033 g, 0.029 mmol) is added. The reaction is heated to 100° C. and stirred for 20 hours under N2. The reaction is cooled, and the solvent is removed in vacuo to give crude 3-{2-methyl-4-[3-methyl-5-(2-pyridin-2-yl-4-trifluoromethyl-phenoxy)-phenoxy]-phenyl}-propionic acid ethyl ester. This ester is dissolved in ethanol (8 mL), treated with 5 N NaOH (2 mL) and heated to reflux until saponification is complete. The mixture is cooled, and the solvent is removed in vacuo to afford a residue that is acidified with 1 N HCl. The mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried (Na2SO4), and the solvent is removed in vacuo to give crude product that is purified by preparative HPLC to afford 0.056 g (38%) of the title compound. 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C29H24NO4F3 507, found 508 (M+1, 100%).

後処理

  1. temperatureheated
  2. temperatureto reflux until saponification
  3. temperatureThe mixture is cooled
  4. customthe solvent is removed in vacuo
  5. customto afford a residue that
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer is dried (Na2SO4)
  8. customthe solvent is removed in vacuo
  9. customto give crude product that
  10. customis purified by preparative HPLC

出典と根拠

ORDレコード
ord-676f772a91d1450883cf8a0d56907ec7
出典データセット
uspto-grants-2009_10
特許番号
US07608639B2

反応ノート

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