Ethyl bromoacetate → {2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-phenoxy}-acetic acid ethyl ester

HRID 1025883ノート

反応式

HRID 1025883 の反応式
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([C:14]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][C:21]=3[O:22][C:23]3[CH:28]=[C:27]([Cl:29])[C:26]([OH:30])=[CH:25][C:24]=3[Cl:31])=[O:15])[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37]>CN(C)C=O>[CH2:39]([O:38][C:36](=[O:37])[CH2:35][O:30][C:26]1[CH:25]=[C:24]([Cl:31])[C:23]([O:22][C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:14]([N:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[N:4]([CH:1]3[CH2:2][CH2:3]3)[CH2:5][CH2:6]2)=[O:15])=[CH:28][C:27]=1[Cl:29])[CH3:40]

参加物

5

反応物 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 53311358(4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-[4-(2,5-dichloro-4-hydroxy-phenoxy)-pyridin-3-yl]-methanone

生成物 1

HCID 53311359{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-phenoxy}-acetic acid ethyl ester収率 81%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 0.15 g (0.33 mmol) (4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-[4-(2,5-dichloro-4-hydroxy-phenoxy)-pyridin-3-yl]-methanone (Example 57) in 2 mL N,N-dimethylformamide was added 0.016 g (0.37 mmol) sodium hydride (60% dispersion in mineral oil, Aldrich, CAS RN 7646-69-7). The reaction mixture was stirred for 15 min. at room temperature before 0.04 mL (0.36 mmol) ethyl bromoacetate (commercially available, CAS RN 105-36-2) were added. After stirring at room temperature for 3 hours the solution was poured on water and extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The resulting powder was purified by silica gel chromatography using a MPLC system (10 g silica gel column, CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 30:70) to give 0.144 g (81%) of the desired compound as a light yellow foam. MS (ESI): m/z=542.123 [M+H]+.

後処理

  1. additionwere added
  2. additionwas poured on water
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. additiontreated with silica gel
  8. customevaporated
  9. customThe resulting powder was purified by silica gel chromatography
  10. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 30:70)

出典と根拠

ORDレコード
ord-8d04303925ae43fbbf7d3e506613c9e7
出典データセット
uspto-grants-2014_05
特許番号
US08729091B2

反応ノート

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