Pioglitazone → 5-(4-(2-(5-Ethylpyridin-2-yl)-2-hydroxyethoxy)benzyl)thiazolidine-2,4-dione

HRID 1482791ノート

反応式

HRID 1482791 の反応式
[CH3:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][O:11][C:12]2[CH:13]=[CH:14][C:15]([CH2:18][CH:19]3[S:25][C:23](=[O:24])[NH:22][C:20]3=[O:21])=[CH:16][CH:17]=2)=[N:7][CH:8]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=[O:29]>C(Cl)Cl>[CH2:2]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]([OH:29])[CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH:19]3[S:25][C:23](=[O:24])[NH:22][C:20]3=[O:21])=[CH:14][CH:13]=2)=[N:7][CH:8]=1)[CH3:1]

参加物

4

反応物 2

HCID 4829PioglitazoneHCID 9845Trifluoroacetic anhydride2 回

生成物 1

HCID 98642685-(4-(2-(5-Ethylpyridin-2-yl)-2-hydroxyethoxy)benzyl)thiazolidine-2,4-dione

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

The N-oxide of racemic pioglitazone (935 mg, 2.54 mmol) was suspended in 12 mL CH2Cl2, then trifluoroacetic anhydride (TFAA, 1.49 mL, 12.69 mmol., 5 equiv.) was added and the reaction mixture was shaken at 50° C. After 24 h, an additional equivalent of TFAA was added and the vial was shaken for another 24 h. After the solvent and excess TFAA were evaporated, the resuting light yellow residue (1.922 g) was dissolved in 5 mL tetrahydrofuran (THF), and next a saturated NaHCO3 aqueous solution was added until gas evolution stopped (4 mL). The resulting solution was diluted with water (10 mL) and the mixture extracted with ethyl acetate (EtOAc, 3×20 mL). The combined organic layers were dried over Na2SO4, filtered and evaporated to provide the alcohol in crude form. The crude alcohol was purified by preparative HPLC (0.1% TFA water/acetonitrile gradient). Fractions containing the pure product were neutralized by addition of triethylamine, combined, and evaporated to provide a residue. The residue was redissolved in EtOAc and the organic layer was washed with brine then dried over Na2SO4. Evaporation of the solvent gave pure 5-({p-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione as a white foam (434.8 mg, 1.17 mmol, 46% yield). LC-MS: 373 (M+1).

後処理

  1. stirringthe vial was shaken for another 24 h
  2. customAfter the solvent and excess TFAA were evaporated
  3. dissolutionthe resuting light yellow residue (1.922 g) was dissolved in 5 mL tetrahydrofuran (THF)
  4. additionnext a saturated NaHCO3 aqueous solution was added until gas evolution
  5. additionThe resulting solution was diluted with water (10 mL)
  6. extractionthe mixture extracted with ethyl acetate (EtOAc, 3×20 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated

出典と根拠

ORDレコード
ord-4d0e5af2bbba486596fa4e16556cc00e
出典データセット
uspto-grants-2016_08
特許番号
US09416117B2

反応ノート

読み込み中…