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 1405342ノート

反応式

HRID 1405342 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-b90d9c3dd0d94febbabe2f4d59e2165c
出典データセット
uspto-grants-2014_12
特許番号
US08916565B2

反応ノート

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