Sodium Carbonate → 1-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol

HRID 410389ノート

反応式

HRID 410389 の反応式
[NH2:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.Br[C:15]1[S:19][C:18]([C:20]2([OH:24])[CH2:23][CH2:22][CH2:21]2)=[N:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[NH2:1][C:2]1[CH:3]=[C:4]([C:15]2[S:19][C:18]([C:20]3([OH:24])[CH2:23][CH2:22][CH2:21]3)=[N:17][CH:16]=2)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1

参加物

5

反応物 3

HCID 10340Sodium CarbonateHCID 27378063-Amino-5-nitrobenzeneboronic acidHCID 584562241-(5-Bromothiazol-2-yl)cyclobutanol

生成物 1

HCID 584562421-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol収率 92%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

To a solution of commercially available (3-amino-5-nitrophenyl)boronic acid (18 g, 99 mmol) and Intermediate 1 (25.5 g, 109 mmol) in DME (360 mL) were added tetrakis(triphenyl-phosphine)palladium(0) (5.72 g, 4.95 mmol) and 2M Na2CO3(aq) (148 mL, 297 mmol), and the mixture was degassed and then heated to 85° C. for 5 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (500 mL) and filtered through Celite (ethyl acetate rinse). The filtrate was washed with brine (300 mL), dried (Na2SO4) and concentrated in vacuo. The impure material was split into two batches, and each purified by Chromatography on silica gel (70:30 to 0:100 hexanes:ethyl acetate) then the product fractions from the two purifications were combined and concentrated in vacuo to provide 26.53 g (91 mmol, 92%) of 1-[5-(3-amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol as a green solid. MS ESI: [M+H]+ m/z 292.0. 1H NMR (DMSO-d6): δ 8.15 (1H, s), 7.54 (1H, s), 7.33 (1H, s), 7.14 (1H, s), 6.58 (1H, s), 6.00 (2H, s), 2.56-2.47 (2H, m), 2.39-2.29 (2H, m), 1.95-1.83 (2H, m).

後処理

  1. customthe mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe mixture was diluted with ethyl acetate (500 mL)
  4. filtrationfiltered through Celite (ethyl acetate rinse)
  5. washThe filtrate was washed with brine (300 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe impure material was split into two batches
  9. customeach purified by Chromatography on silica gel (70:30 to 0:100 hexanes:ethyl acetate)
  10. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-1c11383ee66248e393d3b53507a6a7dc
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

読み込み中…