Hydrogen Peroxide → tert-Butyl 2'-methyl-6'-(trifluoromethyl)-3',4'-dihydro-2'H-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-carboxylate

HRID 1405342노트

반응식

HRID 1405342 반응식
[CH3:1][N:2]1[C:10]2([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[C:6]2=[CH:7][CH:8]=[CH:9][N:5]2[CH2:4][CH2:3]1.[C:23](I)([F:26])([F:25])[F:24].OO>CS(C)=O>[CH3:1][N:2]1[C:10]2([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]2)[C:6]2=[CH:7][CH:8]=[C:9]([C:23]([F:26])([F:25])[F:24])[N:5]2[CH2:4][CH2:3]1

참가 물질

5

반응물 3

HCID 784Hydrogen PeroxideHCID 16843TrifluoroiodomethaneHCID 68153652tert-Butyl 2'-methyl-3',4'-dihydro-2'H-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-carboxylate

생성물 1

HCID 68153221tert-Butyl 2'-methyl-6'-(trifluoromethyl)-3',4'-dihydro-2'H-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-carboxylate수율 64%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

To tert-butyl 2-methylspiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (10.0 g, 32.7 mmol) in DMSO (164 mL) was added ferrous sulfate heptahydrate (9.8 mL of 1.0 M, 9.8 mmol) followed by CF3I (6.41 g, 32.7 mmol) by slow bubbling through the solution and taking the weight difference of the canister. The mixture was cooled with a ice-water bath before H2O2 (3.71 mL of 30% w/v, 32.7 mmol) dropwise over 15 min keeping the internal temperature<20° C. The mixture was poured onto 300 mL of ice water and was extracted with EtOAc (2×400 mL). The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified column chromatography eluting with 0-10% methanol in dichloromethane with 2% iPr2NEt to give tert-butyl 2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (7.8 g, 64%).

후처리

  1. customby slow bubbling through the solution
  2. customthe internal temperature<20° C
  3. extractionwas extracted with EtOAc (2×400 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified column chromatography
  9. washeluting with 0-10% methanol in dichloromethane with 2% iPr2NEt

출처 및 근거

ORD 기록
ord-b90d9c3dd0d94febbabe2f4d59e2165c
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08916565B2

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