Azobisisobutyronitrile → (6S)-5-[(tert-butoxy)carbonyl]-5-azaspiro[2.4]heptane-6-carboxylic acid

HRID 1424674노트

반응식

HRID 1424674 반응식
Br[C:2]1(Br)[C:4]2([CH2:8][C@@H:7]([C:9]([OH:11])=[O:10])[N:6]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:5]2)[CH2:3]1.C[Si]([SiH]([Si](C)(C)C)[Si](C)(C)C)(C)C.CC(N=NC(C#N)(C)C)(C#N)C>C1(C)C=CC=CC=1.CCOC(C)=O>[C:15]([O:14][C:12]([N:6]1[C@H:7]([C:9]([OH:11])=[O:10])[CH2:8][C:4]2([CH2:3][CH2:2]2)[CH2:5]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

참가 물질

6

반응물 3

HCID 6547Azobisisobutyronitrile3회HCID 123134Tris(trimethylsilyl)silane3회HCID 71014840(6S)-1,1-dibromo-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid

생성물 1

HCID 39871141(6S)-5-[(tert-butoxy)carbonyl]-5-azaspiro[2.4]heptane-6-carboxylic acid수율 39%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
110 °C

실험 절차

To a degassed solution of (6S)-1,1-dibromo-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (580 mg, 1.45 mmol) in toluene (6 mL) was added the tris(trimethylsilyl)silane (1.35 mL, 4.36 mmol, 3.0 eq) and AIBN (24 mg, 0.145 mmol, 0.1 eq). The solution was heated at 110° C. for 3 hours. Another batch of tris(trimethylsilyl)silane (0.45 mL 1.45 mmol, 1.0 eq) and AIBN (10 mg) was added. The solution was heated at 110° C. for 2 more hours. A third batch of tris(trimethylsilyl)silane (0.45 mL 1.45 mmol, 1.0 eq) and AIBN (10 mg) was added. The solution was heated at 110° C. for 2 more hours. After being allowed to cool down, the solution was diluted with EtOAc (5 mL). This organic phase was extracted with aqueous K2CO3 (1 M, 10 mL×3). The combined aqueous extractions were cooled (ice/water) and acidified to pH 2 with concentrated HCl. This acidified aqueous phase was extracted with EtOAc (×3), dried (Na2SO4), filtered and evaporated. The residue was dried under vacuum to afford the desired compound as colorless oil (135 mg, 39%).

후처리

  1. temperatureThe solution was heated at 110° C. for 2 more hours
  2. temperatureThe solution was heated at 110° C. for 2 more hours
  3. temperatureto cool down
  4. extractionThis organic phase was extracted with aqueous K2CO3 (1 M, 10 mL×3)
  5. extractionThe combined aqueous extractions
  6. temperaturewere cooled (ice/water)
  7. extractionThis acidified aqueous phase was extracted with EtOAc (×3)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was dried under vacuum

출처 및 근거

ORD 기록
ord-07a3939fab474c8985d8c542be98574b
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927739B2

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