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

HRID 410389노트

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HRID 410389 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1c11383ee66248e393d3b53507a6a7dc
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

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