Chlorotrimethylsilane → 5-[2-Benzyloxy-4-(4-ethylpyridin-2-ylmethyl)-phenyl]-1,1-dioxo-2-(2-trimethylsilanyl-ethyl)-1,2,5-thiadiazolidin-3-one

HRID 1642613

반응식

HRID 1642613 반응식
BrCCBr.C[Si](Cl)(C)C.[CH2:10]([O:17][C:18]1[CH:23]=[C:22]([CH2:24]I)[CH:21]=[CH:20][C:19]=1[N:26]1[S:30](=[O:32])(=[O:31])[N:29]([CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:28](=[O:39])[CH2:27]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.Br[C:62]1[CH:67]=[C:66]([CH2:68][CH3:69])[CH:65]=[CH:64][N:63]=1>CN(C)C(=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:10]([O:17][C:18]1[CH:23]=[C:22]([CH2:24][C:62]2[CH:67]=[C:66]([CH2:68][CH3:69])[CH:65]=[CH:64][N:63]=2)[CH:21]=[CH:20][C:19]=1[N:26]1[S:30](=[O:32])(=[O:31])[N:29]([CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:28](=[O:39])[CH2:27]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

참가 물질

9

반응물 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 41142482-Bromo-4-ethylpyridineHCID 667568095-(2-Benzyloxy-4-iodomethylphenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one

생성물 1

HCID 667566635-[2-Benzyloxy-4-(4-ethylpyridin-2-ylmethyl)-phenyl]-1,1-dioxo-2-(2-trimethylsilanyl-ethyl)-1,2,5-thiadiazolidin-3-one

시약·촉매·용매 3

HCID 23994Zinc촉매2회HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 31374Dimethylacetamide용매3회

반응 조건

온도
120 °C

실험 절차

In pressure vessels, zinc powder (2.145 g, 33 mmol) is dried by heating under vacuum, then cooled, placed under N2, and slurried in N,N-dimethylacetamide (4 mL). To the slurry is added 1,2-dibromoethane (220 μL, 2.55 mmol) and the mixture is heated until boiling. The mixture is allowed to cool, and TMSCl (325 mL, 2.55 mmol) is added, followed by stirring for 30 min. to produce a green solution. To the slurry of activated zinc is added 5-(2-benzyloxy-4-iodomethylphenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (3.0 g, 5.37 mmol) in N,N-dimethylacetamide (5 mL) over 30 min. The organozinc solution is filtered and degassed with N2, then to it is added Pd2(dba)3 (250 mg, 0.275 mmol) and 2-(di-t-butylphosphino)biphenyl (330 mg, 1.1 mmol), followed by degassed 2-bromo-4-ethylpyridine (1.20 g, 6.44 mmol) in N,N-dimethylacetamide. The vessels are sealed and the reaction heated in the microwave in 4 batches, 120° C. for 20 min. The reaction is allowed to cool to ambient temperature, then filtered through Celite. The resulting solutions are combined and diluted with EtOAc (150 mL) and washed with water and brine, then dried over MgSO4. The solvent is removed under reduced pressure and the crude residue is purified via silica gel chromatography using a gradient of 0-75% EtOAc/hexanes to afford the title compound as a colorless oil: MS (M+H)+=616.

후처리

  1. temperatureby heating under vacuum
  2. temperaturecooled
  3. temperaturethe mixture is heated until boiling
  4. temperatureto cool
  5. customto produce a green solution
  6. filtrationThe organozinc solution is filtered
  7. customdegassed with N2
  8. customThe vessels are sealed
  9. temperatureto cool to ambient temperature
  10. filtrationfiltered through Celite
  11. additiondiluted with EtOAc (150 mL)
  12. washwashed with water and brine
  13. dry with materialdried over MgSO4
  14. customThe solvent is removed under reduced pressure
  15. customthe crude residue is purified via silica gel chromatography

출처 및 근거

ORD 기록
ord-68ee025a7425439cb58001f0e1413a76
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08119666B2

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