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

HRID 1424674ノート

反応式

HRID 1424674 の反応式
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]

参加物

6

反応物 3

HCID 6547Azobisisobutyronitrile3 回HCID 123134Tris(trimethylsilyl)silane3 回HCID 71014840(6S)-1,1-dibromo-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid

生成物 1

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

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-07a3939fab474c8985d8c542be98574b
出典データセット
uspto-grants-2015_01
特許番号
US08927739B2

反応ノート

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