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3,5-Dibromopyridine → (3aR,6aS)-tert-butyl 5-(5-bromopyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 1685498
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HRID 1685498 반응식
[CH2:1]1[C@@H:5]2[CH2:6][NH:7][CH2:8][C@@H:4]2[CH2:3][N:2]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[Br:16][C:17]1[CH:18]=[N:19][CH:20]=[C:21](Br)[CH:22]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.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].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[Br:16][C:17]1[CH:22]=[C:21]([N:7]2[CH2:6][C@@H:5]3[CH2:1][N:2]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3][C@@H:4]3[CH2:8]2)[CH:20]=[N:19][CH:18]=1
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참가 물질

8

반응물 3

HCID 693693,5-DibromopyridineHCID 1514452Cis-2-boc-hexahydropyrrolo[3,4-C]pyrroleHCID 23676156Sodium t-butoxide

생성물 1

HCID 44189936(3aR,6aS)-tert-butyl 5-(5-bromopyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate수율 67%

시약·촉매·용매 4

HCID 634876Binap, (A+-)-촉매
HCID 9811564
Bis(dibenzylideneacetone)palladium
촉매
HCID 962Water용매
HCID 1140Toluene용매

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온도
80 °C

실험 절차

The product from Example 1C (1.01 g, 4.76 mmol) and 3,5-dibromopyridine (1.22 g, 5.15 mmol) were dissolved in toluene (20 mL). Pd2(dba)3 (86.8 mg, 0.095 mmol), BINAP (175.0 mg, 0.28 mmol) and sodium tert-butoxide (665.4 mg, 1.460 mmol) were added to the reaction mixture. The reaction was heated to 80° C. for 22 h, then allowed to cool to ambient temperature, diluted with water (100 mL) and extracted with CH2Cl2 (3×100 mL). The organic extracts were combined and washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (EtOAc, Rr=0.33) to afford the title compound as a white solid (1.17 g, 67%). MS (DCI/NH3) m/z 370 (M+H)+.

후처리

  1. temperatureto cool to ambient temperature
  2. extractionextracted with CH2Cl2 (3×100 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by silica gel chromatography (EtOAc, Rr=0.33)

출처 및 근거

ORD 기록
ord-df2f8e3d42694240aa7b1f609d01bfa7
출처 데이터셋
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08148408B2

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